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Despite the growing prevalence of nanoplastics in drinking water distribution systems, the collective influence of nanoplastics and background nanoparticles on biofilm formation and microbial risks remains largely unexplored. Here, we demonstrate that nano-sized polystyrene modified with carboxyl groups (nPS) and background magnetite (nFe 3 O 4 ) nanoparticles at environmentally relevant concentrations can collectively stimulate biofilm formation and prompt antibiotic resistance. Combined exposure of nPS and nFe 3 O 4 by P. aeruginosa biofilm cells stimulated intracellular reactive oxidative species (ROS) production more significantly compared with individual exposure. The resultant upregulation of quorum sensing (QS) and c-di-GMP signaling pathways enhanced the biosynthesis of polysaccharides by 50 %- 66 % and increased biofilm biomass by 36 %- 40 % relative to unexposed control. Consistently, biofilm mechanical stability (measured as Young's modulus) increased by 7.2-9.1 folds, and chemical stress resistance (measured with chlorine disinfection) increased by 1.4-2.0 folds. For P. aeruginosa, the minimal inhibitory concentration of different antibiotics also increased by 1.1-2.5 folds after combined exposure. Moreover, at a microbial community-wide level, metagenomic analysis revealed that the combined exposure enhanced the multi-species biofilm's resistance to chlorine, enriched the opportunistic pathogenic bacteria, and promoted their virulence and antibiotic resistance. Overall, the enhanced formation of biofilms (that may harbor opportunistic pathogens) by nanoplastics and background nanoparticles is an overlooked phenomenon, which may jeopardize the microbial safety of drinking water distribution systems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nanotechnology has opened new doors of exploration, particularly in materials science and healthcare. Magnetic nanoparticles (MNP), the tiny magnets, because of their various properties, have the potential to bring about radical changes in the field of medicine. The distinctive surface chemistry, nontoxicity, biocompatibility, and, in particular, the inducible magnetic moment of magnetic materials has attracted a great deal of interest in morphological structures from a variety of scientific domains. This review presents a concise overview of MNPs and their crucial properties and synthesis routes. It also aims to highlight the continuous synthesis methods available for MNP production. In recent years, the use of computational methods for understanding the behavior of nanoparticles has been on the rise. Thus, we also discuss the numerical models developed to understand how magnetic nanoparticles can be used in magnetic hyperthermia and targeting the Circle of Wilis. With the increasing use of MNPs in biomedical applications, it becomes necessary to understand the mechanisms of toxicity, which are elucidated in this review. The review focuses on the biomedical applications of MNPs in drug delivery, theranostics, and MRI contrasting agents. We anticipate that this article will broaden the perspective on magnetic nanoparticles and help to understand their functionality and applicability better.

Iron oxide nanoparticles (IONPs) have been extensively explored in biomedicine, bio-sensing, hyperthermia, and drug/gene delivery, attributed to their versatile and tunable properties. However, owing to its numerous applications, the functionalization of IONPs with appropriate materials is in demand. To achieve optimal functionalization of IONPs, polydopamine (PDA) was utilized due to its ability to provide a superior functionalized surface, near-infrared light absorption, and adhesive nature to customize desired functionalized IONPs. This notion of involving PDA led to the successful synthesis of magnetite-PDA nanoparticles, where PDA is surface-coated on magnetite (Fe 3 O 4 @PDA). The Fe 3 O 4 @PDA nanoparticles were characterized using techniques like TEM, FESEM, PXRD, XPS, VSM, and FTIR, suggesting PDA's successful attachment with magnetite crystal structure retention. Human serum albumin (HSA), the predominant protein in blood plasma, interacts with the delivered nanoparticles. Therefore, we have employed various spectroscopic techniques, along with cytotoxicity, to inspect the effect of Fe 3 O 4 @PDA NPs on the stability and structure of HSA. The structural alterations were examined using circular dichroism (CD) and synchronous fluorescence spectroscopy (SFS). It has been observed that there are no structural perturbations in the secondary structure of the HSA protein after interaction with Fe 3 O 4 @PDA. Studies using steady-state fluorescence revealed that the inherent fluorescence intensities of HSA were suppressed after interaction with Fe 3 O 4 @PDA. In addition, temperature-dependent fluorescence measurements suggested that the type of quenching consists of both static and dynamic quenching simultaneously. A cytotoxicity study in Drosophila melanogaster larvae revealed no cytotoxic effects but did show a minor genotoxic effect only at higher concentrations.

Examining the critical role of anticoagulants in medical practice, particularly their central function in preventing abnormal blood clotting, is of the utmost importance. However, the study of interactions between blood proteins and alternative anticoagulant nano-surfaces is still understood poorly. In this study, novel approach involving direct functionalisation of magnetic iron oxide nanoparticles (MNPs) as carriers with sulphated dextran (s-dext) is presented, with the aim of evaluating the potential of magnetically-responsive MNPs@s-dext as anticoagulants. The physicochemical characterisation of the synthesised MNPs@s-dext includes crystal structure analysis, morphology study, surface and electrokinetic properties, thermogravimetric analysis and magnetic properties` evaluation, which confirms the successful preparation of the nanocomposite with sulfonate groups. The anticoagulant potential of MNPs@s-dext was investigated using a standardised activated partial thromboplastin time (APTT) test and a modified APTT test with a quartz crystal microbalance with dissipation (QCM-D) which confirmed the anticoagulant effect. Time-resolved solid-liquid interactions between the MNPs@s-dext and model blood proteins bovine serum albumin and fibrinogen were also investigated, to gain insight into their hemocompatibility, and revealed protein-repellence of MNPs@s-dext against blood proteins. The study also addressed comprehensive cytotoxicity studies of prepared nanocomposites, and provided valuable insights into potential applicability of MNPs@s-dext as a promising magnetic anticoagulant in biomedical contexts., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationship that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The rise in cyanobacterial blooms due to eutrophication and climate change has increased cyanotoxin presence in water. Most current water treatment plants do not effectively remove these toxins, posing a potential risk to public health. This study introduces a water treatment approach using nanostructured beads containing magnetic nanoparticles (MNPs) for easy removal from liquid suspension, coated with different adsorbent materials to eliminate cyanotoxins. Thirteen particle types were produced using activated carbon, CMK-3 mesoporous carbon, graphene, chitosan, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-oxidised cellulose nanofibers (TOCNF), esterified pectin, and calcined lignin as an adsorbent component. The particles' effectiveness for detoxification of microcystin-LR (MC-LR), cylindrospermopsin (CYN), and anatoxin-A (ATX-A) was assessed in an aqueous solution. Two particle compositions presented the best adsorption characteristics for the most common cyanotoxins. In the conditions tested, mesoporous carbon nanostructured particles, P1-CMK3, provide good removal of MC-LR and Merck-activated carbon nanostructured particles, P9-MAC, can remove ATX-A and CYN with high and fair efficacy, respectively. Additionally, in vitro toxicity of water treated with each particle type was evaluated in cultured cell lines, revealing no alteration of viability in human renal, neuronal, hepatic, and intestinal cells. Although further research is needed to fully characterise this new water treatment approach, it appears to be a safe, practical, and effective method for eliminating cyanotoxins from water.

Neurogenesis is the process by which new brain cells are formed. This crucial event emerges during embryonic life and proceeds in adulthood, and it could be influenced by environmental pollution. Non-combustion-derived magnetite represents a portion of the coarse particulate matter (PM) contributing to air and water pollution in urban settings. Studies on humans have reported that magnetite and other iron oxides have significant damaging effects at a central level, where these particles accumulate and promote oxidative stress. Similarly, magnetite nanoparticles can cross the placenta and damage the embryo brain during development, but the impact on neurogenesis is still unknown. Furthermore, an abnormal Fe cation concentration in cells and tissues might promote reactive oxygen species (ROS) generation and has been associated with multiple neurodegenerative conditions. In the present study, we used zebrafish as an in vivo system to analyze the specific effects of magnetite on embryonic neurogenesis. First, we characterized magnetite using mineralogical and spectroscopic analyses. Embryos treated with magnetite at sub-lethal concentrations showed a dose-response increase in ROS in the brain, which was accompanied by a massive decrease in antioxidant genes ( sod2 , cat , gsr , and nrf2 ). In addition, a higher number of apoptotic cells was observed in embryos treated with magnetite. Next, interestingly, embryos exposed to magnetite displayed a decrease in neural staminal progenitors ( nestin , sox2 , and pcna markers) and a neuronal marker ( elavl3 ). Finally, we observed significative increases in apoeb (specific microglia marker) and interleukin-1b ( il1b ), confirming a status of inflammation in the brain embryos treated with magnetite. Our study represents the very first in vivo evidence concerning the effects of magnetite on brain development.

Iron-magnetic nanoparticles (Fe-NMPs) are widely used in environmental remediation, while porphyrin-based hybrid materials anchored to silica-coated Fe 3 O 4 -nanoparticles (Fe 3 O 4 -NPs) have been used for water disinfection purposes. To assess their safety on plants, especially concerning potential environmental release, it was investigated for the first time, the impact on plants of a silica-coated Fe 3 O 4 -NPs bearing a porphyrinic formulation (FORM) - FORM@NMP. Additionally, FORM alone and the magnetic nanoparticles without FORM anchored (NH 2 @NMP) were used for comparison. Wheat (Triticum aestivum L.) was chosen as a model species and was subjected to three environmentally relevant doses during germination and tiller development through root application. Morphological, physiological, and metabolic parameters were assessed. Despite a modest biomass decrease and alterations in membrane properties, no major impairments in germination or seedling development were observed. During tiller phase, both Fe 3 O 4 -NPs increased leaf length, and photosynthesis exhibited varied impacts: both Fe 3 O 4 -NPs and FORM alone increased pigments; only Fe 3 O 4 -NPs promoted gas exchange; all treatments improved the photochemical phase. Regarding oxidative stress, lipid peroxidation decreased in FORM and FORM@NMP, yet with increased O 2 -• in FORM@NMP; total flavonoids decreased in NH 2 @NMP and antioxidant enzymes declined across all materials. Phenolic profiling revealed a generalized trend towards a decrease in flavones. In conclusion, these nanoparticles can modulate wheat physiology/metabolism without apparently inducing phytotoxicity at low doses and during short-time exposure. ENVIRONMENTAL IMPLICATION: Iron-magnetic nanoparticles are widely used in environmental remediation and fertilization, besides of new applications continuously being developed, making them emerging contaminants. Soil is a major sink for these nanoparticles and their fate and potential environmental risks in ecosystems must be addressed to achieve more sustainable environmental applications. Furthermore, as the reuse of treated wastewater for agricultural irrigation is being claimed, it is of major importance to disclose the impact on crops of the nanoparticles used for wastewater decontamination, such as those proposed in this work., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Carbon nanotubes are promising materials for biomedical applications like delivery systems and tissue scaffolds. In this paper, magnetic carbon nanotubes (M-CNTs) covered with bovine serum albumin (M-CNTs-BSA) or functionalized with hydrophilic monomers (M-CNTs-HL) were synthesized, characterized, and evaluated concerning their interaction with Caco-2 cells. There is no comparison between these two types of functionalization, and this study aimed to verify their influence on the material's interaction with the cells. Different concentrations of the nanotubes were applied to investigate cytotoxicity, cell metabolism, oxidative stress, apoptosis, and capability to cross biomimetic barriers. The materials showed cytocompatibility up to 100 μg mL -1 and a hemolysis rate below 2 %. Nanotubes' suspensions were allowed to permeate Caco-2 monolayers for up to 8 h under the effect of the magnetic field. Magnetic nanoparticles associated with the nanotubes allowed estimation of permeation through the monolayers, with values ranging from 0.50 to 7.19 and 0.27 to 9.30 × 10 -3  μg (equivalent to 0.43 to 6.22 and 0.23 to 9.54 × 10 -2  % of the initially estimated mass of magnetic nanoparticles) for cells exposed and non-exposed to the magnets, respectively. Together, these results support that the developed materials are promising for applications in biomedical and biotechnological fields., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eduardo Costa Figueiredo reports financial support was provided by Federal University of Alfenas. Mariana Azevedo Rosa reports financial support was provided by Coordination of Higher Education Personnel Improvement. Eduardo Costa Figueiredo reports financial support was provided by Minas Gerais State Foundation of Support to the Research. Eduardo Costa Figueiredo reports financial support was provided by National Council for Scientific and Technological Development. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In recent years, the escalating concerns surrounding environmental pollution and the need for sustainable wastewater treatment solutions have underscored the significance of developing technologies that can efficiently treat wastewater while also reducing negative ecological effects. In this context, our study aims to contribute to the advancement of sustainable technologies for wastewater treatment, by investigating the effects that bare magnetite nanoparticles and those functionalized with the enzyme laccase could have in an aquatic animal, zebrafish, at various life cycle stages. Exposure to magnetite nanoparticles shows some effects on embryo hatching, survival rates, or larval behavior at higher concentrations. For both treatments, the hatching percentages were close to 80% compared to 93% for the control group. At the end of the observations in larvae, survival in all the evaluated groups was higher than 90%. Additionally, we evaluated the accumulation of nanoparticles in various stages of zebrafish. We found that, although there was accumulation during embryonic stages, it did not affect normal development or subsequent hatching. Iron levels in different organs such as gills, muscles, gastrointestinal tract, and brain were also evaluated in adults. Animals treated with a mix of food and nanoparticles at 10 μg/mL (Food group) presented a higher concentration of iron accumulation in muscle, gastrointestinal tract, and gills compared to the untreated control group. Although iron levels increased depending on the dose and exposure method applied, they were not statistically significant from the control groups. Our findings suggest that bionanocomposites evaluated here can be considered safe for removal of contaminants in wastewater without toxic effects or detrimental accumulation fish's health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The applications of magnetic nanoparticles (MNPs) as biocatalysts in different biomedical areas have been evolved very recently. One of the main challenges in this field is to design affective MNPs surfaces with catalytically active atomic centres, while producing minimal toxicological side effects on the hosting cell or tissues. MNPs of vanadium spinel ferrite (VFe 2 O 4 ) are a promising material for mimicking the action of natural enzymes in degrading harmful substrates due to the presence of active V 5+ centres. However, the toxicity of this material has not been yet studied in detail enough to grant biomedical safety. In this work, we have extensively measured the structural, compositional, and magnetic properties of a series of V x Fe 3-x O 4 spinel ferrite MNPs to assess the surface composition and oxidation state of V atoms, and also performed systematic and extensive in vitro cytotoxicity and genotoxicity testing required to assess their safety in potential clinical applications. We could establish the presence of V 5+ at the particle surface even in water-based colloidal samples at pH 7, as well as different amounts of V 2+ and V 3+ substitution at the A and B sites of the spinel structure. All samples showed large heating efficiency with Specific Loss Power values up to 400 W/g (H 0  = 30 kA/m; f = 700 kHz). Samples analysed for safety in human hepatocellular carcinoma (HepG2) cell line with up to 24h of exposure showed that these MNPs did not induce major genomic abnormalities such as micronuclei, nuclear buds, or nucleoplasmic bridges (MNIs, NBUDs, and NPBs), nor did they cause DNA double-strand breaks (DSBs) or aneugenic effects-types of damage considered most harmful to cellular genetic material. The present study is an essential step towards the use of these type of nanomaterials in any biomedical or clinical application., Competing Interests: Declaration of competing interest The authors declare that they do not have any affiliations that would lead to conflicts of interest. There were no financial or non-financial forms of assistance provided by third parties specifically for the conduct of the research presented in this manuscript. The authors have had no financial interests or relationships within the past three years that are related to the subject matter of the manuscript, including advisory roles, consulting, equity ownership, or receipt of non-financial support. None of the co-authors hold any patents or copyrights relevant to the work in this manuscript. There are no additional activities or relationships that the authors need to disclose, which could be perceived as influencing the research or its interpretation., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Nowadays, the unique features of nanoparticles (NPs) have encouraged new applications in different areas including biology, medicine, agriculture, and electronics. Their quick joining into daily life not only enhances the uses of NPs in a wide range of modern technologies but also their release into the aquatic environment causes inevitable environmental concerns. On the other hand boron exhibits key physiological effects on biological systems. This research was designed for evaluating the toxicity of magnetite nanoparticles (Fe 3 O 4 -MNPs) on aquatic organisms and obtaining data for the information gap in this area. In this study, Rainbow trout (Oncorhynchus mykiss) was considered as an aquatic indicator, and trials were designed as Ulexite (a boron mineral, UX) treatment against exposure to Fe 3 O 4 -MNPs. Synthesized and characterized Fe 3 O 4 -MNPs were exposed to rainbow trouts in wide spectrum concentrations (0.005-0.08 mL/L) to analyze its lethal dose (LC 50 ) and cytoprotective properties by UX treatment were assessed against Fe 3 O 4 -MNPs applications for 96 h. For the initial toxicity analysis, hematological parameters (blood cell counts) were examined in experimental groups and micronucleus (MN) assay was performed to monitor nuclear abnormalities after exposure to NPs. Biochemical analyzes in both blood and liver samples were utilized to assess antioxidant/oxidative stress and inflammatory parameters. Also, 8-hydroxy-2'-deoxyguanosine (8-OHdG) assay was used to investigate oxidative DNA lesions and Caspase-3 analysis was performed on both blood and liver tissues to monitor apoptotic cell death occurrence. When antioxidant enzymes in blood and liver tissue were examined, time-dependent decreases in activity were determined in SOD, CAT, GPx, and GSH enzymes, while increased levels of MDA and MPO parameters were observed in respect to Fe 3 O 4 -MNPs exposure. It was found that TNF-α, Il-6 levels were enhanced against Fe 3 O 4 -MNPs treatment, but Nrf-2 levels were decreased at the 46th and 96th h. In the 96th application results, all parameters were statistically significant ( p  < 0.05) in blood and liver tissue, except for the IL-6 results. It was determined that the frequency of MN, the level of 8-OHdG and caspase-3 activity increased in respect to Fe 3 O 4 -MNPs exposure over time. Treatment with UX alleviated Fe3O4-MNPs-induced hematotoxic and hepatotoxic alterations as well as oxidative and genetic damages. Our findings offer strong evidence for the use of UX as promising, safe and natural protective agents against environmental toxicity of magnetite nanoparticles.

Functionalized nanoparticles have been developed for use in nanomedicines for treating life threatening diseases including various cancers. To ensure safe use of these new nanoscale reagents, various assays for biocompatibility or cytotoxicity in vitro using cell lines often serve as preliminary assessments prior to in vivo animal testing. However, many of these assays were designed for soluble, colourless materials and may not be suitable for coloured, non-transparent nanoparticles. Moreover, cell lines are not always representative of mammalian organs in vivo. In this work, we use non-invasive impedance sensing methods with organotypic human liver HepaRG cells as a model to test the toxicity of PEG-Fe 3 O 4 magnetic nanoparticles. We also use Coherent anti-Stokes Raman Spectroscopic (CARS) microscopy to monitor the formation of lipid droplets as a parameter to the adverse effect on the HepaRG cell model. The results were also compared with two commercial testing kits (PrestoBlue and ATP) for cytotoxicity. The results suggested that the HepaRG cell model can be a more realistic model than commercial cell lines while use of impedance monitoring of Fe 3 O 4 nanoparticles circumventing the uncertainties due to colour assays. These methods can play important roles for scientists driving towards the 3Rs principle - Replacement, Reduction and Refinement., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The cytotoxic effects of water-based ferrofluids composed of iron oxide nanoparticles, including magnetite (Fe 3 O 4 ) and maghemite (γ-Fe 2 O 3 ), ranging from 15 to 100 nm, were examined on various lung cancer cells including adenocarcinomic human alveolar basal epithelial cells (A549), nonsmall lung squamous cell carcinoma (H1703), small cell lung cancer cells (DMS 114), and normal bronchial epithelial cells (BEAS-2B). The cytotoxic effect was evaluated both with and without exposure to an alternating magnetic field (AMF). The studies revealed that neither AMF nor iron oxide nanoparticles when tested individually, produced cytotoxic effects on either cancerous or noncancerous cells. However, when applied together, they led to a significant decrease in cell viability and proliferative capacity due to the enhanced effects of magnetic fluid hyperthermia (MFH). The most pronounced effects were found for maghemite (<50 nm) when subjected to an AMF. Notably, A549 cells exhibited the highest resistance to the proposed hyperthermia treatment. BEAS-2B cells demonstrated susceptibility to magnetized iron oxide nanoparticles, similar to the response observed in lung cancer cells. The studies provide evidence that MFH is a promising strategy as a standalone treatment for different types of lung cancer cells. Nevertheless, to prevent any MFH-triggered adverse effects on normal lung cells, targeted magnetic ferrofluids should be designed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Magnetite nanoparticles (MNPs) have been extensively detected in the atmospheric environment and implicated as a prominent threat to atherosclerosis, a chronic vascular inflammatory disease. Due to globalization and economic development, the dramatic shift in diet from traditional to high-fat dietary patterns aggravated atherosclerosis progression induced by environmental factors. However, limited knowledge is available regarding vascular risks and underlying mechanisms of airborne MNPs in high-risk populations with high-fat dietary habits. Herein, we demonstrated that MNPs exerted a proatherogenic effect under high-fat dietary patterns, leading to aortic wall thickening, elastic fiber disorganization, macrophage infiltration, and local inflammation. Based on the correlation analysis between MNPs and PM group, we identified that MNPs might be a key PM component in atherogenic toxicity. MNPs exposure disturbed the dynamic process of lipid metabolism, manifested as aortic lipid accumulation, dyslipidemia, and hepatic lipid metabolism disorder, which was modulated by the JAK-STAT pathway. Overall, these findings provide new insight into understanding the cardiovascular risks and mechanisms of MNPs among high-risk populations., (© 2023 Wiley Periodicals LLC.)

Nanoparticles have been used in neurological research in recent years because of their blood-brain barrier penetration activity. However, their potential neuronanotoxicity remains a concern. In particular, microglia, which are resident phagocytic cells, are mainly exposed to nanoparticles in the brain. We investigated the changes in lysosomal function in silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO 2 (RITC)]-treated BV2 murine microglial cells. In addition, we analyzed amyloid beta (Aβ) accumulation and molecular changes through the integration of transcriptomics, proteomics, and metabolomics (triple-omics) analyses. Aβ accumulation significantly increased in the 0.1 μg/μl MNPs@SiO 2 (RITC)-treated BV2 cells compared to the untreated control and 0.01 μg/μl MNPs@SiO 2 (RITC)-treated BV2 cells. Moreover, the MNPs@SiO 2 (RITC)-treated BV2 cells showed lysosomal swelling, a dose-dependent reduction in proteolytic activity, and an increase in lysosomal swelling- and autophagy-related protein levels. Moreover, proteasome activity decreased in the MNPs@SiO 2 (RITC)-treated BV2 cells, followed by a concomitant reduction in intracellular adenosine triphosphate (ATP). By employing triple-omics and a machine learning algorithm, we generated an integrated single molecular network including reactive oxygen species (ROS), autophagy, lysosomal storage disease, and amyloidosis. In silico analysis of the single triple omics network predicted an increase in ROS, suppression of autophagy, and aggravation of lysosomal storage disease and amyloidosis in the MNPs@SiO 2 (RITC)-treated BV2 cells. Aβ accumulation and lysosomal swelling in the cells were alleviated by co-treatment with glutathione (GSH) and citrate. These findings suggest that MNPs@SiO 2 (RITC)-induced reduction in lysosomal activity and proteasomes can be recovered by GSH and citrate treatment. These results also highlight the relationship between nanotoxicity and Aβ accumulation., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Iron oxide nanoparticles (IONP) are showing promise in many biomedical applications. One of these- magnetic hyperthermia- utilizes externally applied alternating magnetic fields and tumor-residing magnetic nanoparticles to generate localized therapeutic temperature elevations. Magnetic hyperthermia is approved in Europe to treat glioblastoma and is undergoing clinical assessment in the United States to treat prostate cancer. In this study, we performed biodistribution and histological analysis of a new IONP (RCL-01) in Wistar rats. These nanoparticles are currently undergoing clinical assessment in locally advanced pancreatic ductal adenocarcinoma to determine the feasibility of magnetic hyperthermia treatment in this disease. The study presented here aimed to determine the fate of these nanoparticles in vivo and whether this results in organ damage. Wistar rats were injected intravenously with relatively high doses of IONP (30 mg Fe /kg, 45 mg Fe /kg and 60 mg Fe /kg) and compared to a vehicle control to determine the accumulation of iron in organs and whether this resulted in histological changes in these tissues. Dose-dependent increases of iron were observed in the liver, spleen and lungs of IONP-treated animals at 7 days postinjection; however, this did not result in significant histological changes in these tissues. Immunofluorescent imaging determined these nanoparticles are internalized by macrophages in tissue, suggesting they are readily phagocytosed by the reticuloendothelial system for eventual recycling. Notably, no changes in iron or dextran staining were found in the kidneys across all treatment groups, providing evidence for potential renal clearance.

Introduction: One of the major challenges in the clinical translation of nanoparticles is the development of formulations combining favorable efficacy and optimal safety. In the past, iron oxide nanoparticles have been introduced as an alternative for gadolinium-containing contrast agents; however, candidates available at the time were not free from adverse effects., Methods: Following the development of a potent iron oxide-based contrast agent SPION Dex , we now performed a systematic comparison of this formulation with the conventional contrast agent ferucarbotran and with ferumoxytol, taking into consideration their physicochemical characteristics, bio- and hemocompatibility in vitro and in vivo, as well as their liver imaging properties in rats., Results: The results demonstrated superior in vitro cyto-, hemo- and immunocompatibility of SPION Dex in comparison to the other two formulations. Intravenous administration of ferucarbotran or ferumoxytol induced strong complement activation-related pseudoallergy in pigs. In contrast, SPION Dex did not elicit any hypersensitivity reactions in the experimental animals. In a rat model, comparable liver imaging properties, but a faster clearance was demonstrated for SPION Dex ., Conclusion: The results indicate that SPION Dex possess an exceptional safety compared to the other two formulations, making them a promising candidate for further clinical translation., Competing Interests: Dr Domokos Máthé reports being a stakeholder and the CEO from CROmed Ltd, outside the submitted work. Dr Kang H Zheng reports grants from EU - Nanoathero, during the conduct of the study. Prof. Dr Erik Stroes reports personal fees from Amgen, personal fees from Sanofi, personal fees from Astra-Zeneca, personal fees from Novo-Nordisk, grants from Ionis, personal fees from Daiichi-Sankyo, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2023 Unterweger et al.)

Lithium, which has a high industrial value, is an environmental pollutant of concern to those who work with lithium in industry as well as to the general public. Biological parameters such as MDA, 8-OHdG, apoptosis (caspase-3), and acetylcholinesterase (AChE) were studied to determine the toxic effects on the brain tissue of the model organism ( Carassius auratus ) exposed to high dose lithium. According to the results obtained, it was found that lithium exposure caused oxidative stress with an increase in MDA level over time and, accordingly, DNA damage and apoptosis occured in brain tissue. It was also found that a decrease in AChE activity was observed, and the high levels of MDA, 8-OHdG, and caspase-3 activity obtained in brain tissue supported this result. The solid phase extraction (SPE) method was used to effectively remove lithium, which has unfavorable effects on living organisms, from aqueous solutions. In this method, a sawdust loaded with magnetite nanoparticles (MNLS) was prepared as an adsorbent for solid phase extraction by a simple method, and it was characterized. Optimal conditions for the SPE process were defined and it was found that lithium could be removed from solution onto the MNLS surface with a high yield of about 96%. The results of the study are crucial for proposing a simple and applicable high performance method.

A major drawback of nanoparticles (NPs) for biomedical applications is their preferential phagocytosis in immune cells, which can be avoided by surface modifications like PEGylation. Nevertheless, examinations of different polyethylene glycol (PEG) chain lengths on the competence of immune cells as well as possible immunotoxic effects are still sparse. Therefore, primary murine macrophages and dendritic cells were generated and incubated with magnetic nanoporous silica nanoparticles (MNPSNPs) modified with different mPEG chains (2 kDa, 5 kDa, and 10 kDa). Cytotoxicity, cytokine release, and the formation of reactive oxygen species (ROS) were determined. Immune competence of both cell types was examined and uptake of MNPSNPs into macrophages was visualized. Concentrations up to 150 µg/mL MNPSNPs showed no effects on the metabolic activity or immune competence of both cell types. However, ROS significantly increased in macrophages incubated with larger PEG chains, while the concentration of cytokines (TNF-α and IL-6) did not indicate a proinflammatory process. Investigations on the uptake of MNPSNPs revealed no differences in the onset of internalization and the intensity of intracellular fluorescence. The study gives no indication for an immunotoxic effect of PEGylated MNPSNPs. Nevertheless, there is still a need for optimization regarding their internalization to ensure an efficient drug delivery.

Superparamagnetic iron oxide nanoparticles (SPIONs) have gained increasing interest in nanomedicine, but most of those that have entered the clinical trials have been withdrawn due to toxicity concerns. Therefore, there is an urgent need to design low-risk and biocompatible SPION formulations. In this work, we present an original safe-by-design nanoplatform made of silica nanoparticles loaded with SPIONs and decorated with polydopamine (SPIONs@SiO2-PDA) and the study of its biocompatibility performance by an ad hoc thorough in vitro to in vivo nanotoxicological methodology. The results indicate that the SPIONs@SiO 2 -PDA have excellent colloidal stability in serum-supplemented culture media, even after long-term (24 h) exposure, showing no cytotoxic or genotoxic effects in vitro and ex vivo. Physiological responses, evaluated in vivo using Caenorhabditis elegans as the animal model, showed no impact on fertility and embryonic viability, induction of an oxidative stress response, and a mild impact on animal locomotion. These tests indicate that the synergistic combination of the silica matrix and PDA coating we developed effectively protects the SPIONs, providing enhanced colloidal stability and excellent biocompatibility.

The current study evaluates the role of reactive oxygen species (ROS) in bioeffects of magnetite nanoparticles (MNPs), such as bare (Fe3O4), humic acids (Fe3O4-HA), and 3-aminopropyltriethoxysilane (Fe3O4-APTES) modified MNPs. Mössbauer spectroscopy was used to identify the local surrounding for Fe atom/ions and the depth of modification for MNPs. It was found that the Fe3O4-HA MNPs contain the smallest, whereas the Fe3O4-APTES MNPs contain the largest amount of Fe2+ ions. Bioluminescent cellular and enzymatic assays were applied to monitor the toxicity and anti-(pro-)oxidant activity of MNPs. The contents of ROS were determined by a chemiluminescence luminol assay evaluating the correlations with toxicity/anti-(pro-)oxidant coefficients. Toxic effects of modified MNPs were found at higher concentrations (>10−2 g/L); they were related to ROS storage in bacterial suspensions. MNPs stimulated ROS production by the bacteria in a wide concentration range (10−15−1 g/L). Under the conditions of model oxidative stress and higher concentrations of MNPs (>10−4 g/L), the bacterial bioassay revealed prooxidant activity of all three MNP types, with corresponding decay of ROS content. Bioluminescence enzymatic assay did not show any sensitivity to MNPs, with negligible change in ROS content. The results clearly indicate that cell-membrane processes are responsible for the bioeffects and bacterial ROS generation, confirming the ferroptosis phenomenon based on iron-initiated cell-membrane lipid peroxidation.

Magnetic nanoparticles are widely used in biomedicine for MRI imaging and anemia treatment. The aging of these nanomaterials in vivo may lead to gradual diminishing of their contrast properties and inducing toxicity. Here, we describe observation of the full lifecycle of 40-nm magnetic particles from their injection to the complete degradation in vivo and associated impact on the organism. We found that in 2 h the nanoparticles were eliminated from the bloodstream, but their initial biodistribution changed over time. In 1 week, a major part of the nanoparticles was transferred to the liver and spleen, where they degraded with a half-life of 21 days. MRI and a magnetic spectral approach revealed preservation of contrast in these organs for more than 1 month. The particle degradation led to the increased number of red blood cells and blood hemoglobin level due to released iron without causing any toxicity in tissues. We also observed an increase in gene expression level of Fe-associated proteins such as transferrin, DMT1, and ferroportin in the liver in response to the iron particle degradation. A deeper understanding of the organism response to the particle degradation can bring new directions to the field of MRI contrast agent design., (© 2022. The Author(s).)

Magnetite nanoparticles (MNPs) are the most conventional type of iron oxide nanoparticles used in the food industrial processes, removal of heavy metals, and biomedical applications in vivo or in vitro. Until now, there is no sufficient information that can confirm its effect on the body's immune system and reproductive health in males. The purpose of this research is to estimate the immunotoxic and reproductive toxic effects of MNPs in male rats. This study included 36 adult male albino rats divided into three groups. The experimental groups were intraperitoneally injected with MNPs at doses of 5 and 10 mg/kg body weight 3 times/week for 60 days, while the control group was injected with saline solution. MNPs caused a significant decrease in the body weight change of the high-treated group. MNPs produced changes in the lymphocyte proliferation rate which referred to a significant immunotoxic effect measured by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide reduction method. The testicular tissue of male-treated rats showed some moderate and severe degenerative changes. The sperm parameters of count, motility, and viability were significantly decreased. Sperm morphological abnormalities were detected in all treated animals. MNPs produced a significant decrease in testosterone levels, increased the level of malondialdehyde, impaired the activity of the antioxidant enzymes and induced testicular DNA damage. In conclusion, MNPs affected the normal immune state in male rats and facilitated the generation of reactive oxygen species subsequently triggering testicular oxidative stress damages. All these consequences had a negative impact on male reproductive health., (© 2022 Wiley-VCH GmbH.)

The aim of the study is an ecotoxicological assessment of magnetite iron oxide-based nanoparticles (NPs), which have risen in popularity in the last decade, on selected terrestrial and aquatic organisms from various levels of the food chain. In the presented study various organisms, from both the terrestrial and aquatic environment, were used as targets for the assessment of NPs ecotoxicity. Plants (radish, oat), marine bacteria (A. fischeri) and crustacean (H. incongruens) were used to represent producers, decomposers, and consumers, respectively. It was found that examined NPs were harmful (to a different degree) to biota from three different trophic levels. Physicochemical characterization (size/morphology, crystallinity, composition, and magnetic properties) of the tested nanoparticles was performed by: transmission electron microscopy, X-ray diffraction, energy dispersive spectroscopy, and Mossbauer spectroscopy, respectively. Phytotoxicity was evaluated according to the OECD 208 Guideline, while acute and chronic toxicity of NPs was conducted using bioassays employing bacteria and crustacea, respectively. The phytotoxicity of all investigated iron oxide-based NPs was dependent on concentration and type of NPs formulation and was measured via biomass, seed germination, root length, shoot height, and content of plant pigments. Increasing the concentration of NPs increased phytotoxicity and mortality of aquatic organisms. Ecotoxicity of iron oxide/silver was dependent on the size and content of silver. Iron oxide NPs coated with nanosilver in a percentage ratio of 69/31 were found to be the most toxic on tested terrestrial and aquatic biota., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Magnetic nanoparticles (MNps) have become powerful tools for multiple biomedical applications such as hyperthermia drivers, magnetic resonance imaging (MRI) vectors, as well as drug-delivery systems. However, their toxic effects on human health have not yet been fully elucidated, especially in view of their great diversity of surface modifications and functionalizations. Citrate-coating of MNps often results in increased hydrophilicity, which may positively impact their performance as drug-delivery systems. Nonetheless, the consequences on the intrinsic toxicity of such MNps are unpredictable. Herein, novel magnetite (Fe3O4) nanoparticles covered with citrate were synthesized and their potential intrinsic acute toxic effects were investigated using in vitro and in vivo models. The proposed synthetic pathway turned out to be simple, quick, inexpensive, and reproducible. Concerning toxicity risk assessment, these citrate-coated iron oxide nanoparticles (IONps) did not affect the in vitro viability of different cell lines (HaCaT and HepG2). Moreover, the in vivo acute dose assay (OECD test guideline #425) showed no alterations in clinical parameters, relevant biochemical variables, or morphological aspects of vital organs (such as brain, liver, lung and kidney). Iron concentrations were slightly increased in the liver, as shown by Graphite Furnace Atomic Absorption Spectrometry and Perls Prussian Blue Staining assays, but this finding was considered non-adverse, given the absence of accompanying functional/clinical repercussions. In conclusion, this study reports on the development of a simple, fast and reproducible method to obtain citrate-coated IONps with promising safety features, which may be used as a drug nanodelivery system in the short run. (263 words)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Rocha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The core size of iron oxide nanoparticles (IONPs) is a crucial factor defining not only their magnetic properties but also toxicological profile and biocompatibility. On the other hand, particular IONPs may induce different biological response depending on the dose, exposure time, but mainly depending on the examined system. New light on this problem may be shed by the information concerning biomolecular anomalies appearing in various cell lines in response to the action of IONPs with different core diameters and this was accomplished in the present study. Using Raman microscopy we studied the abnormalities in the accumulation of proteins, lipids and organic matter within the nucleus, cytoplasm and cellular membrane of macrophages, HEK293T and U87MG cell line occurring as a result of 24-hour long exposure to PEG-coated magnetite IONPs. The examined nanoparticles had 5, 10 and 30 nm cores and were administered in doses 5 and 25 μg Fe/ml. The obtained results showed significant anomalies in biochemical composition of macrophages and the U87MG cells, but not the HEK293T cells, occurring as a result of exposure to all of the examined nanoparticles. However, IONPs with 10 nm core diminished the accumulation of biomolecules in cells only when they were administered at a larger dose. The Raman spectra recorded for the macrophages subjected to 30 nm IONPs and for the U87MG cells exposed to 5 and 10 nm showed the presence of additional bands in the wavenumber range 1700-2400 cm -1 , probably resulting from the appearance of Fe adducts within cells. Our results indicate, moreover, that smaller IONPs may be effectively internalized into the U87MG cells, which points at their diagnostic/therapeutic potential in the case of glioblastoma multiforme., (Copyright © 2022. Published by Elsevier B.V.)

Fine particulate matter (PM) is a leading environmental cause for the increased morbidity and mortality of atherosclerosis (AS) worldwide, but little is known about the toxic component and disturbance of PM exposure on foam cell formation, a crucial pathological process in AS. Airborne magnetite nanoparticles (NPs) have been reported to be detected in human serum, which inevitably encounter with macrophages in atherosclerotic plaques, thus throwing potential disturbance on the formation of macrophage-derived foam cells. Here we comprehensively unveiled that the environmental concentrations of PM exposure triggered and potentiated the formation of macrophage-derived foam cells using both real-ambient PM-exposed mice and AS mice models, including high-fat diet-fed mice and apolipoprotein E-deficient mice. The in vitro model further defined the dose-dependent response of PM treatment on foam cell formation. Interestingly, airborne magnetite NPs rather than nonmagnetic NPs at the same concentration were demonstrated to be the key toxic component of PM in the promoted foam cell formation. Furthermore, magnetite NPs exposure led to abnormal cholesterol accumulation in macrophages, which was attributed to the attenuation of cholesterol efflux and enhancement of lipoprotein uptake, but independent of cholesterol esterification. The in-depth data revealed that magnetite NPs accelerated the protein ubiquitination and subsequent degradation of SR-B1, a crucial transporter of cholesterol efflux. Collectively, these findings for the first time identified magnetite NPs as one key toxic component of PM-promoted foam cell formation, and provided new insight of abnormal cholesterol metabolism into the pathogenesis of PM-induced AS., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Dendrimers and dendrons offer a high surface area and nanoscale size and magnetic nanoparticles can be easily detected and manipulated due to their magnetic properties. The aim of the present study is to investigate the in vitro toxicity of Polyester-8-hydroxyl-1-carboxyl bis-MPA dendron, generation 3 (bis-MPA), Hyperbranched G4-PEG6k-OH (PEG) dendrimer and magnetite nanoparticle (Fe 3 O 4 ), in human lymphocytes. Cell viability assays were performed on non-stimulated and lipopolysaccharide (LPS) stimulated lymphocytes, after exposure to various concentrations of the nanoparticles, using the Trypan blue assay, Flow Cytometry with 7-Amino Actinomycin D fluorescent dye (7-AAD), as well as the 3-[4,5-dimethylthiazol-2-yl] 2,5 diphenyl tetrazolium bromide (MTT) colorimetric method. The results collectively showed that after 24 h both the dendron and dendrimer at 50 μM concentration exhibited low cytotoxicity to non-stimulated and stimulated lymphocytes. Magnetite nanoparticle (Fe 3 O 4 ) in concentrations 50-1000 μg/mL revealed negligible cytotoxicity to stimulated and non-stimulated lymphocytes. Moreover, the amount of intercellular Reactive Oxygen Species with or without treatment was assessed by means of the DCFH-DA to evaluate the presence of any oxidative stress. We propose herein simple cytotoxicity tests which indicate that these nanoparticles, after further studying, can serve as ideal drug carriers., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Due to unique reaction conditions of the acoustic cavitation process, ultrasound-assisted synthesis of nanoparticles has attracted increased research attention. In this study, we demonstrate the effect of ultrasonic irradiation on the crystallinity, stability, biocompatibility, and magnetic properties of chitosan-coated superparamagnetic iron oxide nanoparticles (CS-SPIONs). CS solution and colloidal suspension of SPIONs were mixed and sonicated using an ultrasonic probe of 1.3 cm tip size horn, frequency (20 kHz), and power (750 W). Different samples were sonicated for 1.5, 5, and 10 min with corresponding acoustic powers of 67, 40 and 36 W, and the samples were denoted S 1.5, S 5, and S 10 , respectively. The samples were characterized using X-ray diffractometer (XRD), Energy dispersive X-ray (EDX), Transmission electronic microscope (TEM), Fourier transform infrared spectroscopy (FTIR), Zeta sizer, and vibrating sample magnetometer (VSM). Cell cytotoxicity and cell uptake were investigated with human embryonic kidney 293 (HEK-293) cells through MTT assay and Prussian blue staining, respectively. The sharp peaks of the XRD pattern were disappearing with an increase in the sonication period but a decrease in acoustic power. EDX analysis also demonstrates that atomic and weight percentages of the various elements in the samples were decreasing with an increase in the sonication period. However, the Zeta potential (ζ) values increase with an increase in the sonication period.The saturation magnetization (M s ) of the S 1.5 before and after the coating is 62.95 and 86.93 emu/g, respectively. Cell cytotoxicity and uptake of the S 1.5 show that above 70% of cells were viable at the highest concentration and the longest incubation duration. Importantly, the CS-SPIONs synthesized by the sonochemical method are non-toxic and biocompatible., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The diagnosis of the dynamics, accumulation, and engraftment of transplanted stem cells in vivo is essential for ensuring the safety and the maximum therapeutic effect of regenerative medicine. However, in vivo imaging technologies for detecting transplanted stem cells are not sufficient at present. We developed nanohybrid particles composed of dendron-baring lipids having two unsaturated bonds (DLU2) molecules, quantum dots (QDs), and magnetic nanoparticles in order to diagnose the dynamics, accumulation, and engraftment of transplanted stem cells, and then addressed the labeling and in vivo fluorescence and magnetic resonance (MR) imaging of stem cells using the nanohybrid particles (DLU2-NPs). Five kinds of DLU2-NPs (DLU2-NPs-1-5) composed of different concentrations of DLU2 molecules, QDs525, QDs605, QDs705, and ATDM were prepared. Adipose tissue-derived stem cells (ASCs) were labeled with DLU2-NPs for 4 h incubation, no cytotoxicity or marked effect on the proliferation ability was observed in ASCs labeled with DLU2-NPs (640- or 320-fold diluted). ASCs labeled with DLU2-NPs (640-fold diluted) were transplanted subcutaneously onto the backs of mice, and the labeled ASCs could be imaged with good contrast using in vivo fluorescence and an MR imaging system. DLU2-NPs may be useful for in vivo multimodal imaging of transplanted stem cells.

As nanoparticles (NPs) can access the brain and impact on CNS function, novel in vitro models for the evaluation of NPs-induced neurotoxicity are advocated. Three-dimensional spheroids of primary neuron-like cells (hNLCs) of human origin have been generated, from differentiation of human umbilical cord mesenchymal stem cells (MSCs). The study evaluated Fe 3 O 4 NP impact on the differentiation process by applying the challenge at complete 3D hNLC spheroid formation (after 4 days, T4) or at beginning of neurogenic induction/simultaneously 3D forming (T0). Different endpoints were monitored over time (up to 10 days): spheroid growth, size, morphology, ATP, cell death, neuronal markers (β-Tub III, MAP-2, and NSE), NP uptake. At T0 application, a marked concentration- and time-dependent cell mortality occurred: effect started early (day 2) and low concentration (1 μg/ml) and exacerbated (80% mortality) after prolonged time (day 6) and increased concentrations (50 μg/ml). ATP was strikingly affected. All neuronal markers were downregulated, and spheroid morphology altered in a concentration-dependent manner (from ≥5 μg/ml) after day 2. Fe 3 O 4 NPs applied at complete 3D formation (T4) still induced adverse effects although less severe: cell mortality (20-60%) and ATP content decrease (10-40%) were observed in a concentration-dependent manner (from ≥ 5 μg/ml). A neuronal-specific marker effect and spheroid size reduction from 25 μg/ml without morphology alteration were evidenced. This finding provides additional information on neurotoxic effects of Fe 3 O 4 NPs in a new 3D hNLC spheroid model derived from MSCs that could find a consistent application as in a testing strategy serving in first step hazard identification for correct risk assessment., (© 2022 John Wiley & Sons, Ltd.)

Magnetic nanoparticles (NPs) are suitable candidates for various medical and biological applications, despite some concerns that they may have negative impacts on human health. In this study, the toxicity effects of magnetic NPs consisting of α"-Fe 16 N 2 captured and bioaccumulated by the nematode Caenorhabditis elegans ( C. elegans ) in the early larval stage are evaluated. The choice of α"-Fe 16 N 2 NPs is based on their good structural stability when stored in saline solution and high magnetic performance. The uptake and bioaccumulation of α"-Fe 16 N 2 NPs in intestinal cells of C. elegans was evidenced by transmission electron microscopy. After exposure to NPs up to 40 mg mL -1 , C. elegans larval development, survival, feeding behavior, defecation cycles, movement and reproduction were monitored. C. elegans survival and other monitored behavioral evolutions do not show significant changes, except for a slight statistical reduction in the reproductive profile. Therefore, the present results are promising and very encouraging for investigations of applications of α"-Fe 16 N 2 NPs in the biomedical area.

Surface-active and water-soluble magnetic nanoparticles (NPs) were synthesized in the presence of a series of amphiphilic molecules of different functional groups to determine the hemolytic response and their ability to extract blood cells across the interface and aqueous bulk while maintaining minimum hemolysis. Amphiphilic molecules such as Gemini surfactants of strong hydrophobicity and low hydrophilic-lipophilic balance produced surface-active magnetic NPs, which were highly cytotoxic even when placed at the blood suspension (aqueous)-air interface. A similar behavior was shown by water-soluble magnetic NPs produced using monomeric ionic and nonionic surfactants and different amino acids. The NPs produced using mild biological surfactants and mono- and oligosaccharides of the same functional group proved to be excellent blood cell extractors with minimum hemolysis. α/β-cyclodextrin and dextrose-stabilized magnetic NPs induced negligible hemolysis and extracted more than 50% of blood cells. The results showed that nontoxic magnetic NPs are excellent blood cell extractors from the blood suspension when tagged with amphiphilic molecules possessing good biocompatibility with cell membranes without inducing hemolysis. The work highlights the biological applicability of nontoxic magnetic NPs at biointerfaces and in blood suspensions.

The use of nanoparticles (NPs) is rapidly expanding; there is a critical need for efficient assays to first determine the potential toxicity of NPs before their use in human applications. Magnetite nanoparticles (Fe 3 O 4 NPs) have tremendous applications which include cell separation, arsenic removal from water and DNA separation. Spherically shaped Fe 3 O 4 NPs with sizes ranging from 23 to 30 nm were used in this study. The housefly, Musca domestica is the most common fly species. It is present worldwide and considered to be an important medical insect which can carry and transmit over 100 human pathogens and zoonotic agents. It has been used in this study to assess Fe 3 O 4 NPs toxicity and give us an overview of their impact. The larvicidal activity of Fe 3 O 4 NPs was tested against the third instar larvae of M. domestica. We investigated the effects of six varying concentrations (15, 30, 45, 60, 75 and 90 μg/mL) used under laboratory conditions in two differential application assays: contact and feeding. The LC 50 value for Fe 3 O 4 NPs was 60 and 75 μg/mL by feeding and contact, respectively. To investigate the toxicity effects of Fe 3 O 4 NPs on houseflies, morphological and histoarchitectural changes in larvae, pupae and adult flies were analyzed. NP exposure caused morphological abnormalities of larvae and pupae as well as larval pupal intermediates, and deformed adult with crumpled wings. Also, some adults couldn't emerge and remained in their puparia. The histological examinations showed that Fe 3 O 4 NPs caused severe tissue damage especially in the cuticle and the digestive system. Thus, besides affecting the organ of first contact (digestive system), remote organs such as the integument are also targeted by Fe 3 O 4 NPs suggesting a systemic impact on fly development and physiology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We designed amine-functionalized nanocrystalline cellulose grafted folic acid/magnetic nanoparticles (AF-NCC/Fe 3 O 4 NPs) against folate receptors for targeted delivery of doxorubicin (DOX). Toxicity is a major side effect of DOX, damaging vital organs such as the heart, kidney, and liver; for example, it causes dilated cardiomyopathy and hepatotoxicity. Accordingly, we aimed to reduce this adverse effect and increase the targeted delivery of DOX to the right point of cancer cells by using the unique features of cancer cells. The characterizations were approved in each step using Fourier transform infrared (FTIR), scanning electron microscope (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), energy dispersive X-ray (EDX), zeta potential, and dynamic light scattering (DLS) analysis techniques. Encapsulation efficacy of AF-NCC/Fe 3 O 4 NPs was 99.6%; drug release investigations showed excellent stability in physiological conditions (pH ∼ 7.4) and a high release rate in the low pH condition of cancer environments (pH ∼ 5.0). The hemolysis assay and Masson's trichrome and hematoxylin and eosin (H&E) staining results showed that the nanocarrier was entirely biocompatible. In vitro cell viability study approved that the designed nanocarrier increased the therapeutic effects of DOX on Saos-2 cells. The cellular internalization results displayed a high percentage of uptake within 2 h. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was applied for the evaluation of tumor protein p53 (p53), p21, and Bcl-2-associated X protein (Bax). DOX exerted its effects through DNA damage and oxidative stress that led to p53 upregulation, and p53 inhibited cell cycle progression. This arrest initiated apoptosis and inhibited cell migration. In summary, encapsulating DOX in AF-NCC/Fe 3 O 4 NPs dramatically decreases the toxic effects of this chemotherapeutic agent on vital organs, especially on the heart. This smart nanocarrier increases the delivery of DOX using acid folic on its surface and also enhances the DOX release in the acidic environment of cancer cells. DOX exerts its therapeutic effects by the initiation of apoptosis and inhibition of migration., (Copyright © 2021. Published by Elsevier B.V.)

Phenolic compounds (like 4-nitrophenol) and dyes (like methyl orange) are common by-products discharged by many industries as wastes; they are toxic and may induce discomfort and irritation in humans when ingested. Most of these compounds can be made less toxic through catalytic degradation. Metal oxide nanoparticles are found to have high catalytic activity and can degrade toxic phenolic compounds and dyes. In the current study, pomegranate rind extract was used for the green synthesis of iron oxide nanoparticles that exhibited an octahedron morphology revealed by scanning electron microscopy analysis. Energy dispersive x-ray analysis showed 47.96% content of Fe (by weight); high resolution-transmission electron microscopy analysis confirmed that the nanoparticles had a particle size of 22.54 ± 4.13 nm. The particles were further characterized by x-ray diffraction, fourier transform-infrared spectroscopy, vibrating sample magnetometer, and thermogravimetric analysis. The nanoparticle proved to be efficient in reducing 4-nitrophenol and methyl orange. It was also found to be non-toxic towards murine macrophages, RAW 264.7 with good ROS-scavenging potential compared to control., (© 2021 IOP Publishing Ltd.)

Sonodynamic therapy (SDT), presenting spatial and temporal control of ROS generation triggered by ultrasound field, has attracted considerable attention in tumor treatment. However, its therapeutic efficacy is severely hindered by the intrinsic hypoxia of solid tumor and the lack of smart design in material band structure. Here in study, fine α-Fe 2 O 3 nanoparticles armored with Pt nanocrystals (α-Fe 2 O 3 @Pt) was investigated as an alternative SDT agent with ingenious bandgap and structural design. The Schottky barrier, due to its unique heterostructure, suppresses the recombination of sono-induced electrons and holes, enabling superior ROS generation. More importantly, the composite nanoparticles may effectively trigger a reoxygenation phenomenon to supply sufficient content of oxygen, favoring the ROS induction under the hypoxic condition and its extra role played for ultrasound imaging. In consequence, α-Fe 2 O 3 @Pt appears to enable effective tumor inhibition with imaging guidance, both in vitro and in vivo. This study has therefore demonstrated a highly potential platform for ultrasound-driven tumor theranostic, which may spark a series of further explorations in therapeutic systems with more rational material design., (© 2021. The Author(s).)

In Asia, including Taiwan, malignant tumors such as Hepatocellular carcinoma (HCC) one of the liver cancer is the most diagnosed subtype. Magnetic resonance imaging (MRI) has been a typical diagnostic method for accurately diagnosing HCC. When it is difficult to demonstrate non-enhanced MRI of tumors, radiologists can use contrast agents (such as Gd 3+ , Fe 3 O 4 , or FePt) for T1-weighted and T2-weighted imaging remain in the liver for a long time to facilitate diagnosis via MRI. However, it is sometimes difficult for T2-weighted imaging to detect small tumor lesions because the liver tissue may absorb iron ions. This makes early cancer detection a challenging goal. This challenge has prompted current research to create novel nanocomposites for enhancing the noise-to-signal ratio of MRI. To develop a method that can more efficiently diagnose and simultaneously treat HCC during MRI examination, we designed a functionalized montmorillonite (MMT) material with a porous structure to benefit related drugs, such as mitoxantrone (MIT) delivery or as a carrier for the FePt nanoparticles (FePt NPs) to introduce cancer therapy. Multifunctional FePt@MMT can simultaneously visualize HCC by enhancing MRI signals, treating various diseases, and being used as an inducer of magnetic fluid hyperthermia (MFH). After loading the drug MIT, FePt@MMT-MIT provides both MFH treatment and chemotherapy in one nanosystem. These results ultimately prove that functionalized FePt@MMT-MIT could be integrated as a versatile drugs delivery system by combining with MRI, chemotheraeutic drugs, and magnetic guide targeting., (© 2021. The Author(s).)

Acute ischemic stroke has become the major cause of mortality and disability worldwide. Following ischemic stroke, the reperfusion injury is mainly mediated by the burst of reactive oxygen and nitrogen species (RONS). Therefore, blocking the excessive production or removing RONS holds great promise as a potential therapeutic strategy. Herein, we developed a Co-doped Fe 3 O 4 nanozyme that is capable of scavenging H 2 O 2 , O 2 •- , • NO, and ONOO- in vitro and in vivo and provides neuroprotection against ischemic stroke. In vitro experiments showed that pre-incubation with the Co-Fe 3 O 4 nanozyme could prevent neurotoxicity and neuroinflammation induced by H 2 O 2 or lipopolysaccharide, respectively, in HT22 cells. After intravenous administration, the Co-Fe 3 O 4 nanozyme showed no signs of toxicity in peripheral organs of C57BL/6J mice, even after prolonged delivery for 4 weeks. In permanent photothrombotic stroke model and transient middle cerebral artery occlusion stroke model, the Co-Fe 3 O 4 nanozyme specifically accumulated in the infarct rim at 72 h post-stroke and was endocytosed by neurons, astrocytes, microglia, and endothelial cells. Importantly, the Co-Fe 3 O 4 nanozyme delivery reduced the infarct volume in both stroke models. The observation that the Co-Fe 3 O 4 nanozyme was efficacious in two well-characterized ischemic stroke models provides strong evidence that it represents a powerful tool for targeting oxidative and nitrosative stress in the ischemic brain.

The development of multifunctional nanoplatforms has been recognized as a promising strategy for potent photodynamic theranostics. Aggregation-induced emission (AIE) photosensitizers undergoing Type-I reactive oxygen species (ROS) generation pathway appear as potential candidates due to their capability of hypoxia-tolerance, efficient ROS production, and fluorescence imaging navigation. To further improve their performance, a facile and universal method of constructing a type of glutathione (GSH)-depleting and near-infrared (NIR)-regulated nanoplatform for dual-modal imaging-guided photodynamic therapy (PDT) is presented. The nanoplatforms are obtained through the coprecipitation process involving upconversion nanoparticles (UCNPs) and AIE-active photosensitizers, followed by in situ generation of MnO 2 as the outer shell. The introduction of UCNPs actualizes the NIR-activation of AIE-active photosensitizers to produce ·OH as a Type-I ROS. Intracellular upregulated GSH-responsive decomposition of the MnO 2 shell to Mn 2+ realizes GSH-depletion, which is a distinctive approach for elevating intracellular ·OH. Meanwhile, the generated Mn 2+ can implement T 1 -weighted magnetic resonance imaging (MRI) in specific tumor sites, and mediate the conversion of intracellular H 2 O 2 to ·OH. These outputs reveal a triple-jump ·OH production, and this approach brings about distinguished performance in FLI-MRI-guided PDT with high-efficacy, which presents great potential for future clinical translations., (© 2021 Wiley-VCH GmbH.)

This work is devoted to studying the effects of non-magnetic shell coating on nanoparticles in a low frequency alternating magnetic field (LF AMF) on tumor cells in vitro. Two types of iron oxide nanoparticles with the same magnetic core with and without silica shells were synthesized. Nanoparticles with silica shells significantly decreased the viability of PC3 cancer cells in a low frequency alternating magnetic field according to the cytotoxicity test, unlike uncoated nanoparticles. We showed that cell death results from the intracellular membrane integrity failure, and the calcium ions concentration increase with the subsequent necrosis. Transmission electron microscopy images showed that the uncoated silica nanoparticles are primarily found in an aggregated form in cells. We believe that uncoated nanoparticles lose their colloidal stability in an acidic endosomal environment after internalization into the cell due to surface etching and the formation of aggregates. As a result, they encounter high endosomal macromolecular viscosity and become unable to rotate efficiently. We assume that effective rotation of nanoparticles causes cell death. In turn, silica shell coating increases nanoparticles stability, preventing aggregation in endosomes. Thus, we propose that the colloidal stability of magnetic nanoparticles inside cells is one of the key factors for effective magneto-mechanical actuation., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: One of the major abiotic stressors that have a serious effect on plant growth and productivity worldwide is the salinity of soil or irrigation water. The effect of foliar application of magnetite nanoparticles (size = 22.05 nm) at different concentrations (0, 0.25, 0.5, and 1.0 ppm) was investigated to improve salinity tolerance in two wheat cultivars, namely, Misr1 (Tolerant) and Gimmeza11 (Sensitive). Moreover, toxicological investigations of magnetite oxide nanoparticle in Wistar albino rats were estimated., Results: The magnetite nanoparticles positively affected growth, chlorophyll, and enzymatic antioxidants such as superoxide dismutase (SOD), stimulating reduced glutathione and improving the aggregation of several polypeptide chains that may be linked to the tolerance of saline stress. In contrast, magnetite nanoparticles reduced malondialdehyde (MDA). Inverse sequence-tagged repeat (ISTR) assay of DNA molecular marker showed the change in band numbers with the highest polymorphic bands with 90% polymorphism at primer F3, B5 and 20 positive bands in Gimmeza11 with 0.5 ppm magnetite nanoparticles. In the median lethal dose (LD 50 ) study, no rats died after the oral administration of magnetite nanoparticle at different doses. Therefore, the iron oxide nanoparticle was nontoxic when administered orally by gavage., Conclusion: Magnetite nanoparticles partially helped to alleviate the effects of salt stress by activating growth, chlorophyll content, SOD, glutathione, and soluble proteins in two wheat cultivars (Misr1 and Gimmeza11) and decreasing MDA content. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Preventing deep bacterial infection and simultaneously enhancing osteogenic differentiation are in great demand for osteomyelitis. Microwave (MW) dynamic therapy is attracting attention due to its excellent penetration ability, but the mechanism of MW-induced reactive oxygen species (ROS) is still unknown. Herein, MW-responsive engineered pseudo-macrophages (M-Fe 3 O 4 /Au nanoparticles (NPs)) are fabricated to clear Staphylococcus aureus infections and induce M2 polarization of macrophages to improve osteogenic differentiation of bone marrow mesenchymal stem cells (MSCs) under MW irradiation. Fe 3 O 4 /Au NPs can generate ·O 2 - and heat under MW irradiation in a saline solution, and the mechanism is put forward via finite element modeling and density functional theory calculations. Due to the gap plasmon, electromagnetic hotspots are produced at Fe 3 O 4 -Au interface at 2.45 GHz. Because of these induced electromagnetic hotspots, the sodium species is field-ionized and subsequently reacts with oxygen to produce ·O 2 - . Meanwhile, the Fe 3 O 4 /Au NPs have a stronger ability than Fe 3 O 4 NPs to fix oxygen, favoring the production of ROS. Additionally, MW-treated macrophages diminish to secrete inflammatory cytokines, resulting in the decrease of ROS production in MSCs and thus enhancing their osteogenic differentiation. These engineered pseudo-macrophages will be promising for effectively treating bacterial infections and promoting osteoblast differentiation simultaneously in deep tissues under MW irradiation., (© 2021 Wiley-VCH GmbH.)

Active targeted therapy for bowel cancer using untethered microrobots has attracted extensive attention. However, traditional microrobots face challenges, such as issues of mobility, biocompatibility, drug loading, sustained-release capabilities, and targeting accuracy. Here, we propose an untethered triple-configurational magnetic robot (TCMR) that is composed of three geometrically nested parts: actuation and guarding, anchoring and seeding, and drug release part. A targeting magnetic driving system actuates the TCMR along the predetermined trajectory to the target position. The pH-sensitive actuation and guarding part formed by electrodeposition is degraded in the intestinal environment and separates from the two other parts. A majority of magnetic nanoparticles encapsulated in this part are retrieved. The anchoring and seeding part anchors the lesion area and seeds the drug release part in the gaps of intestinal villi by hydrolysis. Ultimately, the drug release part containing the therapeutic completes the sustained release to prolong the duration of the therapeutic agent. Cytotoxicity and therapeutic tests reveal that TCMRs are biocompatible and suitable for targeted therapy and have good therapeutic performance. The newly designed TCMR will provide new ideas for targeted therapy, thus expanding the application scope of robotics technology in the biomedical field.

Over the last decade, upconversion nanoparticles (UCNP) have been widely investigated in nanomedicine due to their high potential as imaging agents in the near-infrared (NIR) optical window of biological tissues. Here, we successfully develop active targeted UCNP as potential probes for dual NIR-NIR fluorescence and radioactive-guided surgery of prostate-specific membrane antigen (PSMA)(+) prostate cancers. We designed a one-pot thermolysis synthesis method to obtain oleic acid-coated spherical NaYF 4 :Yb,Tm@NaYF 4 core/shell UCNP with narrow particle size distribution (30.0 ± 0.1 nm, as estimated by SAXS analysis) and efficient upconversion luminescence. Polyethylene glycol (PEG) ligands bearing different anchoring groups (phosphate, bis- and tetra-phosphonate-based) were synthesized and used to hydrophilize the UCNP. DLS studies led to the selection of a tetra-phosphonate PEG (2000) ligand affording water-dispersible UCNP with sustained colloidal stability in several aqueous media. PSMA-targeting ligands ( i.e. , glutamate-urea-lysine derivatives called KuEs) and fluorescent or radiolabelled prosthetic groups were grafted onto the UCNP surface by strain-promoted azide-alkyne cycloaddition (SPAAC). These UCNP, coated with 10 or 100% surface density of KuE ligands, did not induce cytotoxicity over 24 h incubation in LNCaP-Luc or PC3-Luc prostate cancer cell lines or in human fibroblasts for any of the concentrations evaluated. Competitive binding assays and flow cytometry demonstrated the excellent affinity of UCNP@KuE for PSMA-positive LNCaP-Luc cells compared with non-targeted UCNP@CO 2 H. Furthermore, the binding of UCNP@KuE to prostate tumour cells was positively correlated with the surface density of PSMA-targeting ligands and maintained after 125 I-radiolabelling. Finally, a preliminary biodistribution study in LNCaP-Luc-bearing mice demonstrated the radiochemical stability of non-targeted [ 125 I]UCNP paving the way for future in vivo assessments.

Hydrogels often have poor mechanical properties which limit their application in load-bearing tissues such as muscle and cartilage. In this work, a near-infrared light-triggered stretchable thermal-sensitive hydrogel with ultra-high drug loading was developed by a combination of natural polymeric nanocrystals, a network of synthetic thermo-responsive polymer, and magnetic Fe 3 O 4 nanoparticles. The hydrogels comprise cellulose nanocrystals (CNCs) decorated with Fe 3 O 4 nanoparticles (Fe 3 O 4 /CNCs) dispersed homogeneously in poly(N-isopropylacrylamide) (PNIPAm) networks. The composite hydrogels exhibit an extensibility of 2200%. Drug loading of vancomycin (VCM) reached a high value of 10.18 g g -1 due to the dispersion of Fe 3 O 4 /CNCs and the interactions between the CNCs and the PNIPAm network. Importantly, the hydrogels demonstrated a thermo-response triggered by NIR, with the temperature increasing from 26 to 41 °C within 60 s. The hydrogels have high biocompatibility evidenced by cell proliferation tests, illustrating that these hydrogels are promising as dressings for wound closure, and wound healing., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Nanoparticles have been studied for brain imaging, diagnosis, and drug delivery owing to their versatile properties due to their small sizes. However, there are growing concerns that nanoparticles may exert toxic effects in the brain. In this study, we assessed direct nanotoxicity on microglia, the resident macrophages of the central nervous system, and indirect toxicity on neuronal cells exerted by silica-coated magnetic nanoparticles containing rhodamine B isothiocyanate dye [MNPs@SiO 2 (RITC)]., Methods: We investigated MNPs@SiO 2 (RITC)-induced biological changes in BV2 murine microglial cells via RNA-sequencing-based transcriptome analysis and gas chromatography-mass spectrometry-based intracellular and extracellular amino acid profiling. Morphological changes were analyzed by transmission electron microscopy. Indirect effects of MNPs@SiO 2 (RITC) on neuronal cells were assessed by Transwell-based coculture with MNPs@SiO 2 (RITC)-treated microglia. MNPs@SiO 2 (RITC)-induced biological changes in the mouse brain in vivo were examined by immunohistochemical analysis., Results: BV2 murine microglial cells were morphologically activated and the expression of Iba1, an activation marker protein, was increased after MNPs@SiO 2 (RITC) treatment. Transmission electron microscopy analysis revealed lysosomal accumulation of MNPs@SiO 2 (RITC) and the formation of vesicle-like structures in MNPs@SiO 2 (RITC)-treated BV2 cells. The expression of several genes related to metabolism and inflammation were altered in 100 µg/ml MNPs@SiO 2 (RITC)-treated microglia when compared with that in non-treated (control) and 10 µg/ml MNPs@SiO 2 (RITC)-treated microglia. Combined transcriptome and amino acid profiling analyses revealed that the transport of serine family amino acids, including glycine, cysteine, and serine, was enhanced. However, only serine was increased in the growth medium of activated microglia; especially, excitotoxic D-serine secretion from primary rat microglia was the most strongly enhanced. Activated primary microglia reduced intracellular ATP levels and proteasome activity in cocultured neuronal cells, especially in primary cortical neurons, via D-serine secretion. Moreover, ubiquitinated proteins accumulated and inclusion bodies were increased in primary dopaminergic and cortical neurons cocultured with activated primary microglia. In vivo, MNPs@SiO 2 (RITC), D-serine, and ubiquitin aggresomes were distributed in the MNPs@SiO 2 (RITC)-treated mouse brain., Conclusions: MNPs@SiO 2 (RITC)-induced activation of microglia triggers excitotoxicity in neurons via D-serine secretion, highlighting the importance of neurotoxicity mechanisms incurred by nanoparticle-induced microglial activation., (© 2021. The Author(s).)

Magnetic Fe 3 O 4 nanoparticles (MNPs) are often used to design agents enhancing contrast in magnetic resonance imaging (MRI) that can be considered as one of the efficient methods for cancer diagnostics. At present, increasing the specificity of the MRI contrast agent accumulation in tumor tissues remains an open question and attracts the attention of a wide range of researchers. One of the modern methods for enhancing the efficiency of contrast agents is the use of molecules for tumor acidic microenvironment targeting, for example, pH-low insertion peptide (pHLIP). We designed novel organosilicon MNPs covered with poly(ethylene glycol) (PEG) and covalently modified by pHLIP. To study the specific features of the binding of pHLIP-modified MNPs to cells, we also obtained nanoconjugates with Cy5 fluorescent dye embedded in the SiO 2 shell. The nanoconjugates obtained were characterized by transmission electron microscopy (TEM), attenuated total reflection (ATR), diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), dynamic light scattering (DLS), UV and fluorescence spectrometry, thermogravimetric analysis (TGA), CHN elemental analyses, and vibrating sample magnetometry. Low cytotoxicity and high specificity of cellular uptake of pHLIP-modified MNPs at pH 6.4 versus 7.4 (up to 23-fold) were demonstrated in vitro. The dynamics of the nanoconjugate accumulation in the 4T1 breast cancer orthotopically grown in BALB/c mice and MDA-MB231 xenografts was evaluated in MRI experiments. Biodistribution and biocompatibility studies of the obtained nanoconjugate showed no pathological change in organs and in the blood biochemical parameters of mice after MNP administration. A high accumulation rate of pHLIP-modified MNPs in tumor compared with PEGylated MNPs after their intravenous administration was demonstrated. Thus, we propose a promising approach to design an MRI agent with the tumor acidic microenvironment targeting ability.

Magnetic iron oxide nanocrystals (MIONs) are established as potent theranostic nanoplatforms due to their biocompatibility and the multifunctionality of their spin-active atomic framework. Recent insights have also unveiled their attractive near-infrared photothermal properties, which are, however, limited by their low near-infrared absorbance, resulting in noncompetitive photothermal conversion efficiencies (PCEs). Herein, we report on the dramatically improved photothermal conversion of condensed clustered MIONs, reaching an ultrahigh PCE of 71% at 808 nm, surpassing the so-far MION-based photothermal agents and even benchmark near-infrared photothermal nanomaterials. Moreover, their surface passivation is achieved through a simple self-assembly process, securing high colloidal stability and structural integrity in complex biological media. The bifunctional polymeric canopy simultaneously provided binding sites for anchoring additional cargo, such as a strong near-infrared-absorbing and fluorescent dye, enabling in vivo optical and photoacoustic imaging in deep tissues, while the iron oxide core ensures detection by magnetic resonance imaging. In vitro studies also highlighted a synergy-amplified photothermal effect that significantly reduces the viability of A549 cancer cells upon 808 nm laser irradiation. Integration of such-previously elusive-photophysical properties with simple and cost-effective nanoengineering through self-assembly represents a significant step toward sophisticated nanotheranostics, with great potential in the field of nanomedicine.

Efficient capture and release of circulating tumor cells play an important role in cancer diagnosis, but the limited affinity of monovalent adhesion molecules in existing capture technologies leads to low capture efficiency, and the captured cells are difficult to be separated. Inspired by the phenomenon that the long tentacles of jellyfish contain multiple adhesion domains and can effectively capture moving food, we have constructed a biomimetic recognition strategy to capture and release tumor cells. In details, gold-coated magnetic nanomaterials (Au@Fe 3 O 4 NPs) were first prepared and characterized by scanning electron microscopy, UV-vis absorption spectra, and Zeta potential. Then, the DNA primers modified on Au@Fe 3 O 4 nanoparticles can be extended to form many radialized DNA products by rolling circle amplification. These long DNA products resemble jellyfish tentacles and contain multivalent aptamers that can be extended into three dimensions to increase the accessibility of target cells, resulting in efficient, simple, rapid, and specific cells capture. The capture efficiencies are no less than 92% in PBS buffer and 77% in blood. Subsequently, DNase I was selected to degrade biomimetic tentacles to release the captured tumor cells with high viability. This release strategy can not only improve cell viability, but also reduce a tedious release process and unnecessary costs. We believe that the proposed method can be expanded for the capture and release of various tumor cells and will inspire the development of circulating tumor cells analysis. A biomimetic recognition strategy for capture and release of circulating tumor cells has been developed. This method modified specific P1 DNA primers on Au@Fe 3 O 4 NPs to form many radialized DNA products by rolling circle amplification. These products can efficiently capture CTCs since it contains multiple aptamers with a multivalent binding capacity. This make it a promising tool to capture and release of other tumor cells, and will inspire the development of CTC analysis.