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Osteoporosis is a metabolic disorder that leads to deterioration of bones. The major challenges confronting osteoporosis therapy include early-stage detection and regular disease monitoring. The present studies employed D-aspartic acid octapeptide (-D-Asp-) 8 as bone-targeting peptide for evaluating osteoporosis manifestation, and superparamagnetic iron oxide nanoparticles (SPIONs) as nanocarriers for MRI-aided diagnosis. Thermal decomposition technique was employed to synthesize SPIONs, followed by surface-functionalization with hydrophilic ligands. Failure mode effect analysis and factor screening studies were performed to identify concentrations of SPIONs and ligand as critical material attributes, and systematic optimization was subsequently conducted employing face-centered cubic design. The optimum formulation was delineated using desirability function, and design space demarcated with 178.70 nm as hydrodynamic particle size, -24.40 mV as zeta potential, and 99.89 % as hydrophilic iron content as critical quality attributes. XRD patterns ratified lattice structure and SQUID studies corroborated superparamagnetic properties of hydrophilic SPIONs. Bioconjugation of (-D-Asp-) 8 with SPIONs (1:1) was confirmed using UV spectroscopy, FTIR and NMR studies. Cell line studies indicated successful targeting of SPIONs to MG-63 human osteoblasts, ratifying enormous bone-targeting and safety potential of peptide-tethered SPIONs as MRI probes. In vivo MRI imaging studies in rats showcased promising contrast ability and safety of peptide-conjugated SPIONs., 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.)

Iron oxide nanoparticles (IONPs) have useful properties, such as strong magnetism and compatibility with living organisms which is preferable for medical applications such as drug delivery and imaging. However, increasing use of these materials, especially in medicine, has raised concerns regarding potential risks to human health. In this study, IONPs were coated with silicon dioxide (SiO 2 ), citric acid (CA), and polyethylenimine (PEI) to enhance their dispersion and biocompatibility. Both coated and uncoated IONPs were assessed for genotoxic effects on Drosophila melanogaster. Results showed that uncoated IONPs induced genotoxic effects, including mutations and recombinations, while the coated IONPs demonstrated reduced or negligible genotoxicity. Additionally, bioinformatic analyses highlighted potential implications of induced recombination in various cancer types, underscoring the importance of understanding nanoparticle-induced genomic instability. This study highlights the importance of nanoparticle coatings in reducing potential genotoxic effects and emphasizes the necessity for comprehensive toxicity assessments in nanomaterial research., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ayca Erdem Unsar reports financial support was provided by Akdeniz University. 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 Elsevier B.V. All rights reserved.)

The adsorption of proteins onto the surface of nanoparticle (NP) leads to the formation of the so-called "protein corona" as consisting both loosely and tightly bound proteins. It is well established that the biological identity of NPs that may be acquired after exposure to a biological matrix is mostly provided by the components of the hard corona as the pristine surface is generally less accessible for binding. For that reason, the isolation and the characterisation of the NP-corona complexes and identification of the associated biomolecules can help in understanding its biological behaviour. Established methods for the isolation of the NP-HC complexes are time-demanding and can lead to different results based on the isolation method applied. Herein, we have developed a fast and simple method using ferromagnetic beads isolated from commercial MACS column and used for the isolation of superparamagnetic NP following exposure to different types of biological milieu. We first demonstrated the ability to easily isolate superparamagnetic iron oxide NPs (IONPs) from different concentrations of human blood plasma, and also tested the method on the corona isolation using more complex biological matrices, such as culture medium containing pulmonary mucus where the ordinary corona methods cannot be applied. Our developed method showed less than 20% difference in plasma corona composition when compared with centrifugation. It also showed effective isolation of NP-HC complexes from mucus-containing culture media upon comparing with centrifugation and MACS columns, which failed to wash out the unbound proteins. Our study was supported with a full characterisation profile including dynamic light scattering, nanoparticle tracking analysis, analytical disk centrifuge, and zeta potentials. The biomolecules/ proteins composing the HC were separated by vertical gel electrophoresis and subsequently analysed by liquid chromatography-tandem mass spectrometry. In addition to our achievements in comparing different isolation methods to separate IONPs with corona from human plasma, this is the first study that provides a complete characterisation profile of particle protein corona after exposure in vitro to pulmonary mucus-containing culture media., 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. Colorobbia is a private company that synthetised the nanomaterials used for this study., (Copyright © 2023. Published by Elsevier Inc.)

The surface modification of magnetite nanoparticles (Fe 3 O 4 NPs) is a promising approach to obtaining biocompatible and multifunctional nanoplatforms with numerous applications in biomedicine, for example, to fight cancer. However, little is known about the effects of Fe 3 O 4 NP-associated reductive stress against cancer cells, especially against chemotherapy-induced drug-resistant senescent cancer cells. In the present study, Fe 3 O 4 NPs in situ coated by dextran (Fe 3 O 4 @Dex) and glucosamine-based amorphous carbon coating (Fe 3 O 4 @aC) with potent reductive activity were characterized and tested against drug-induced senescent breast cancer cells (Hs 578T, BT-20, MDA-MB-468, and MDA-MB-175-VII cells). Fe 3 O 4 @aC caused a decrease in reactive oxygen species (ROS) production and an increase in the levels of antioxidant proteins FOXO3a, SOD1, and GPX4 that was accompanied by elevated levels of cell cycle inhibitors (p21, p27, and p57), proinflammatory (NFκB, IL-6, and IL-8) and autophagic (BECN1, LC3B) markers, nucleolar stress, and subsequent apoptotic cell death in etoposide-stimulated senescent breast cancer cells. Fe 3 O 4 @aC also promoted reductive stress-mediated cytotoxicity in nonsenescent breast cancer cells. We postulate that Fe 3 O 4 NPs, in addition to their well-established hyperthermia and oxidative stress-mediated anticancer effects, can also be considered, if modified using amorphous carbon coating with reductive activity, as stimulators of reductive stress and cytotoxic effects in both senescent and nonsenescent breast cancer cells with different gene mutation statuses.

Using targeted drug delivery systems has emerged as a promising approach to increase the efficacy of chemotherapy, particularly in combination with gene therapy. The overexpression of miR-21 plays a crucial role in colorectal cancer (CRC) progression, and targeted inhibition of miR-21 offers significant potential for enhancing CRC chemotherapy outcomes. In this study, a theranostic system based on mesoporous silica and superparamagnetic iron oxide nanoparticles (SPION@MSNs) was synthesized as a core-shell structure. After loading epirubicin (EPI) in the open pores of MSN, the plasmid expressing anti-miR-21 (pDNA) covered the outer surface with the help of a ZIF-8 (zeolitic imidazolate framework-8) film. Afterward, polyethylene glycol (PEG) and AS1411 aptamer were conjugated to the surface to improve the protective, biocompatibility, and targeting abilities of the nanocarrier. Moreover, the physicochemical characteristics as well as the loading capacity and release profile of EPI and pDNA were fully evaluated. The uptake of the nanoparticles by CRC and normal cell lines in addition to the anticancer effects related to targeted combinational therapy were investigated in vitro . Finally, in vivo tests were performed on BALB/c mice bearing colorectal tumors to evaluate the effectiveness of the targeted nanoparticles, their possible side effects, and also their application in fluorescence and magnetic imaging in vivo . The successful synthesis of SPION@MSN-EPI/pDNA-ZIF-8-PEG-Apt nanoparticles (∼68 nm) and good loading efficiency and controlled release of EPI and pDNA were confirmed. Moreover, hemolysis and gel retardation assays demonstrated the biocompatibility and plasmid protection. Cellular uptake and expression of copGFP illustrated selective entry and transient transfection of targeted nanoparticles, consistent with the cytotoxicity results that indicated the synergistic effects of chemo-gene therapy. The results of animal studies proved the high antitumor efficiency of targeted nanoparticles with minimal tissue damage, which was in line with fluorescence and magnetic imaging results. The novel synthesized nanoparticles containing SPION@MSN-ZIF-8 were suitable for CRC theranostics, and the combined approach of chemo-gene therapy suppressed the tumor more effectively.

The use of conventional methods for the treatment of cancer, such as chemotherapy or radiotherapy, and approaches such as brachytherapy in conjunction with the unique properties of nanoparticles could enable the development of novel theranostic agents. The aim of our current study was to evaluate the potential of iron oxide nanoparticles, coated with alginic acid and polyethylene glycol, functionalized with the chemotherapeutic agent doxorubicin and the monoclonal antibody bevacizumab, to serve as a nanoradiopharmaceutical agent against breast cancer. Direct radiolabeling with the therapeutic isotope Lutetium-177 ( 177 Lu) resulted in an additional therapeutic effect. Functionalization was accomplished at high percentages and radiolabeling was robust. The high cytotoxic effect of our radiolabeled and non-radiolabeled nanostructures was proven in vitro against five different breast cancer cell lines. The ex vivo biodistribution in tumor-bearing mice was investigated with three different ways of administration. The intratumoral administration of our functionalized radionanoconjugates showed high tumor accumulation and retention at the tumor site. Finally, our therapeutic efficacy study performed over a 50-day period against an aggressive triple-negative breast cancer cell line (4T1) demonstrated enhanced tumor growth retention, thus identifying the developed nanoparticles as a promising nanobrachytherapy agent against breast cancer.

Biodistribution tracks compounds or molecules of interest in vivo to understand a compound's anticipated efficacy and safety. Nanoparticles deliver nucleic acid and drug payloads and enhance tumor permeability due to multiple properties such as high surface area to volume ratio, surface functionalization, and modifications. Studying the in vivo biodistribution of nanoparticles documents the effectiveness and safety of nanoparticles and facilitates a more application-driven approach for nanoparticle development that allows for more successful translation into clinical use. In this study, we present a relatively simple method to determine the biodistribution of magnetic iron nanoparticles in mice. In vitro, cells take up branched amphiphilic peptide-coated magnetic nanobeads (BAPc-MNBs) like their counterparts, i.e., branched amphiphilic peptide capsules (BAPCs) with a hollow water-filled core. Both BAPc-MNBs and BAPCs have widespread applications as a nanodelivery system. We evaluated the BAPc-MNBs tissue distribution in wild-type mice injected intravenously (i.v.), intraperitoneally (i.p.), or orally gavaged to understand the biological interactions and to further the development of branched amphiphilic peptide-based nanoparticles. The magnetic nanoparticles allowed collection of the BAPc-MNBs from multiple organs by magnetic bead sorting, followed by a high-throughput screening for iron content. When injected i.v., nanoparticles were distributed widely to various organs before elimination from the system via the intestines in feces. The spleen accumulated the highest amount of BAPc-MNBs in mice administered NPs via i.v. and i.p. but not via oral gavage. Taken together, these data demonstrate that the magnetic sorting not only allowed quantification of the BAPc-MNBs but also identified the distribution of BAPc-MNBs after distinct administration methods.

Aim: To synthesize HER2 aptamer-conjugated iron oxide nanoparticles with a coating of poly(2-(dimethylamino) ethyl methacrylate)-poly(2-methacryloyloxyethylphosphorylcholine) block copolymer (IONPPPs). Methods: Characterization covered molecular structure, chemical composition, thermal stability, magnetic characteristics, aptamer interaction, crystalline nature and microscopic features. Subsequent investigations focused on IONPPPs for in vitro cancer cell identification. Results: Results demonstrated high biocompatibility of the diblock copolymer with no significant toxicity up to 150 μg/ml. The facile coating process yielded the IONPP complex, featuring a 13.27 nm metal core and a 3.10 nm polymer coating. Functionalized with a HER2-targeting DNA aptamer, IONPPP enhanced recognition in HER2-amplified SKBR3 cells via magnetization separation. Conclusion: These findings underscore IONPPP's potential in cancer research and clinical applications, showcasing diagnostic efficacy and HER2 protein targeting in a proof-of-concept approach.

The industry transfer of laboratory-use magnetic separation is still hampered by the lack of suitable nanoparticles, both in terms of their features and large-scale availability. Surface Active Maghemite Nanoparticles (SAMNs) characterized by a unique surface chemistry, low environmental impact, scalable synthesis and functionalization were used to develop a bio-inspired lactoferrin (LF) recognition system. Based on the LF affinity for DNA, a self-assembly process was optimized for obtaining a SAMN@DNA hybrid displaying chemical and colloidal stability and LF specificity. SAMN@DNA was successfully tested for the affinity purification of LF from crude bovine whey. Advantages, such as high selectivity and loading capacity, nanoparticle re-usability, outstanding purity (96 ± 1%), preservation of protein conformation and short operational time, were highlighted. Finally, scalability was demonstrated by an automatic system performing continuous purification of LF from 100 liters day -1 of whey. This study responds to essential prerequisites, such as efficiency, re-usability and industrialization feasibility., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alessandro Cecconello reports financial support was provided by Government of Italy Ministry of Education University and Research. Federica Tonolo reports financial support was provided by Government of Italy Ministry of Education University and Research. Fabio Vianello reports financial support was provided by veneto region. Massimiliano Magro has patent #Apparatus and method for a separation through magnetic nanoparticles CN 107635666 B. issued to Luca Bettinsoli, Riccardo Braga, Mauro Braga, Andrea Gatti, Massimiliano Magro, Fabio Vianello., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Fluorine magnetic resonance imaging ( 19 F MRI) has emerged as an attractive alternative to conventional 1 H MRI due to enhanced specificity deriving from negligible background signal in this modality. We report a dual nanoparticle conjugate (DNC) platform as an aptamer-based sensor for use in 19 F MRI. DNC consists of core-shell nanoparticles with a liquid perfluorocarbon core and a mesoporous silica shell ( 19 F-MSNs), which give a robust 19 F MR signal, and superparamagnetic iron oxide nanoparticles (SPIONs) as magnetic quenchers. Due to the strong magnetic quenching effects of SPIONs, this platform is uniquely sensitive and functions with a low concentration of SPIONs (4 equivalents) relative to 19 F-MSNs. The probe functions as a "turn-on" sensor using target-induced dissociation of DNA aptamers. The thrombin binding aptamer was incorporated as a proof-of-concept (DNC Thr ), and we demonstrate a significant increase in 19 F MR signal intensity when DNC Thr is incubated with human α-thrombin. This proof-of-concept probe is highly versatile and can be adapted to sense ATP and kanamycin as well. Importantly, DNC Thr generates a robust 19 F MRI "hot-spot" signal in response to thrombin in live mice, establishing this platform as a practical, versatile, and biologically relevant molecular imaging probe., (© 2023 Wiley-VCH GmbH.)

The present study describes the synthesis of pure and Cu doped α-Fe 2 O 3 nanoparticles (with various concentrations of Copper 1, 3, 6, and 9 wt%) by conventional chemical precipitation technique and examines their structural, morphological, optical, magnetic, and antibacterial capabilities. The XRD pattern of pure and Cu-doped α-Fe 2 O 3 nanoparticles exhibit rhombohedral structure and the estimated crystalline sizes were ranged from 39 to 58 nm. It is discovered that the estimated density dislocations linked to the agglomeration/cluster formations diminish when interstitial vacancies are filled with copper. The obtained bandgap from Tauc's plot, 2.07 eV of pure α-Fe 2 O 3 is found to less than Cu doped α-Fe 2 O 3 nanoparticles (2.9-3.4 eV), due to the structural changes and the tailing of localised states into deep bandgap energy levels. The intense blue emission bands (410-490 nm) arised due to the movement of trapped electrons from the donor level to the valance band and broad green emission bands (522-560 nm) are due to deep level CuO defect to the Fe 2 O 3 . The fundamental stretching of Fe-O vibrations and the presence of Cu in prepared samples were identified in FTIR and Raman spectra. SEM micrograph shows the uniform distribution of spherical nanoparticles with size ranged from 39 to 61 nm, which is in good accord with XRD studies. Further, the magnetic characteristics of the pure and Cu-doped α-Fe 2 O 3 samples were assessed using a vibrating sample magnetometer (VSM); the ensuing hysteresis loop of the Cu-doped α-Fe 2 O 3 displays weaker ferromagnetic behaviour. In the present investigations, the disc diffusion technique has been used to examine the antibacterial activity. Thus, the results of antibacterial activities demonstrated that at concentrations of 200 and 500 μg/ml of pure and Cu-doped α-Fe 2 O 3 NPs, the highest zone of inhibition was found against gram (+ve) positive bacteria and was followed by the gram (-ve) negative bacteria's., 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 B.V. All rights reserved.)

Iron oxide nanoparticles (Fe 3 O 4 NPs) have attracted great attention due to their extensive applications, which warranted their environmental concerns. Although recent advances have proposed the relevance of Fe 3 O 4 NPs to cardiovascular disease, the intrinsic mechanisms underlying the effects of NPs remain indistinct. ApoE -/- mice were chosen as a long-term exposure model to explore the immanent association between respiratory exposure to Fe 3 O 4 NPs and the development of cardiovascular diseases. Pulmonary exposure to 20 nm and 200 nm Fe 3 O 4 NP S resulted in significant lung injury, and pulmonary histopathological examination displayed inflammatory cell infiltration, septal thickening and alveolar congestion. Intriguingly, liver iron deposition and variations in the hepatic lipid homeostasis were found in Fe 3 O 4 NPs-exposed mice, eventually leading to dyslipidemia, hinting the potential cardiovascular toxicity of Fe 3 O 4 NPs. In addition, we not only found that Fe 3 O 4 NPs exposure increased aortic plaque area, but also increased M1 macrophages in the plaque, which yielding plaque vulnerability in ApoE -/- mice Of note, 20 nm Fe 3 O 4 NPs showed enhanced capability on the progression of atherosclerosis than 200 nm Fe 3 O 4 NPs. This study may propose the potential mechanism for adverse cardiovascular disease induced by Fe 3 O 4 NPs and provide convincing evidence for the safety evaluation of Fe 3 O 4 NPs., 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 Ltd. All rights reserved.)

Aquatic environments are complicated systems that contain different types of nanoparticles (NPs). Nevertheless, recent studies of NP toxicity, and especially those that have focused on bioaccumulation have mostly investigated only a single type of NPs. Assessments of the environmental risks of NPs that do not consider co-exposure regimes may lead to inaccurate conclusions and ineffective environmental regulation. Thus, the present study examined the effects of differently sized silica NPs (SiO 2 NPs) on the uptake of iron oxide NPs (Fe 2 O 3 NPs) by the zooplankton Daphnia magna . Both SiO 2 NPs and Fe 2 O 3 NPs were well dispersed in the experimental medium without significant heteroaggregation. Although all three sizes of SiO 2 NPs inhibited the uptake of Fe 2 O 3 NPs, the underlying mechanisms differed. SiO 2 NPs smaller than the average mesh size (∼200 nm) of the filtering apparatus of D. magna reduced the accumulation of Fe 2 O 3 NPs through uptake competition, whereas larger SiO 2 NPs inhibited the uptake of Fe 2 O 3 NPs mainly by reducing the water filtration rate of the daphnids. Overall, in evaluations of the risks of NPs in the natural environment, the different mechanisms underlying the effects of NPs of different sizes on the uptake of dissimilar NPs should be considered.

This work is aimed at studying the drug delivery applications of iron oxide (Fe 3 O 4 ) nanoparticles with strontium (Sr) doping with varying molar ratios prepared by the co-precipitation route. The impact of increased strontium content on the particle size and magnetic properties was investigated. The impending of these nanoparticles for drug loading, drug release, and their respective cytotoxicity was also inspected.First, iron oxide nanoparticles were doped with various amounts of strontium, from 0.25, 0.50, and 0.75, to 1 mol using co-precipitation method. These synthesized nanoparticles were characterized by XRD, SEM, EDX, VSM, and FTIR for evaluating crystal structure, phase purity, morphology, composition, magnetic properties, and functional groups, respectively. Drug loading and drug release properties were determined using UV-vis spectroscopy, whereas MTT assay evaluated cytotoxicity. Colloidal stability was assessed using zeta potential in PBS solution.The findings confirmed the successful doping of iron oxide with strontium via XRD and EDX. SEM results confirmed spherical morphology for all and needle-like structure for 1 mol strontium doped sample. For VSM results, a single domain structure was established. It was also observed that the drug encapsulation efficiency increases with increased strontium content. Cytotoxicity results by MTT assay revealed increased cytotoxicity with increasing nanoparticle concentration, and ibuprofen-loaded nanoparticles showed higher cytotoxicity than un-loaded nanoparticles at the same concentration. Zeta potential results showed colloidal stability of iron oxide nanoparticles increased by the addition of strontium.This study provided predominantly comparison of the cytotoxicity of ibuprofen-loaded and non-loaded nanoparticles on Hep-2 cancer cells at similar concentrations for the first time for both Fe 3 O 4 particles and Sr-doped Fe 3 O 4 nanoparticles and enclosed the impact of increasing Sr doping content on Fe 3 O 4 nanoparticles., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nowadays, there is a growing interest in multifunctional therapeutic agents as valuable tools to improve and expand the applicability field of traditional bioactive compounds. In this context, the synthesis and main characteristics of dextran-coated iron oxide nanoparticles (IONP-Dex) loaded with both an antioxidant, protocatechuic acid (PCA), and an antibiotic, ceftazidime (CAZ) or levofloxacin (LEV) are herein reported for the first time, with emphasis on the potentiation effect of PCA on drugs activity. All nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, vibrating sample magnetometry, differential scanning calorimetry and dynamic light scattering. As evidenced by DPPH method, IONP-Dex loaded with PCA and LEV had similar antioxidant activity like those with PCA only, but higher than PCA and CAZ loaded ones. A synergy of action between PCA and each antibiotic co-loaded on IONP-Dex has been highlighted by an enhanced activity against reference bacterial strains, such as S. aureus and E. coli after 40 min of incubation. It was concluded that PCA, which is the main cause of the antioxidative properties of loaded nanoparticles, further improves the antimicrobial activity of IONP-Dex nanoparticles when was co-loaded with CAZ or LEV antibiotics. All constructs also showed a good biocompatibility with normal human dermal fibroblasts., 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 B.V. All rights reserved.)

Background: As a broad-spectrum antitumorigenic agent, doxorubicin (DOX) is commonly used as a chemotherapeutic drug for treating osteosarcoma (OS). Still, it is associated with significant cell toxicity and ineffective drug delivery, whereas the zeolite imidazolate framework is extensively applied in the biomedical field as a carrier owing to its favorable biocompatibility, high porosity, and pH-responsiveness. Therefore, we need to develop a drug delivery platform that can effectively increase the antitumorigenic effect of the loaded drug and concurrently minimize drug toxicity., Methods: In this study, a Fe 3 O 4 @ZIF-8 nanocomposite carrier was prepared with ZIF-8 as the shell and encapsulated with Fe3O4 by loading DOX to form DOX- Fe 3 O 4 @ZIF-8 (DFZ) drug-loaded magnetic nanoparticles. Then, we characterized and analyzed the morphology, particle size, and characteristics of Fe 3 O 4 @ZIF-8 and DFZ by TEM, SEM, and Malvern. Moreover, we examined the inhibitory effects of DFZ in vitro and in vivo. Meanwhile, we established a tumor-bearing mouse model, evaluating its tumor-targeting by external magnetic field guidance., Results: DFZ nanoparticles possessed have a size of ~110 nm, with an encapsulation rate of 21% and pH responsiveness. DFZ exerted a superior cytostatic effect and apoptosis rate on K7M2 cells in vitro compared to DOX(p<0.01). In animal experiments, DFZ offers up to 67% tumor inhibition and has shown a superior ability to induce apoptosis than DOX alone in TUNEL results(p<0.01). Tumor-targeting experiments have validated that DFZ can be effectively accumulated in the tumor tissue and enhance anticancer performance., Conclusion: In summary, the DFZ nano-delivery system exhibited a more substantial anti-tumorigenic effect as well as superior active tumor targeting of DOX- Fe 3 O 4 @ZIF-8 compared to that of DOX alone in terms of biocompatibility, drug loading capacity, pH-responsiveness, tumor-targeting, and anti-tumorigenic effect, indicating its chemotherapeutic application potential., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Wu et al.)

Activatable dual-modal molecular imaging probes present a promising tool for the diagnosis of malignant tumors. However, synchronously enhancing dual-modal imaging signals under a single stimulus is challenging. Herein, we propose an activatable bimodal probe that integrates aggregation-induced emission luminogens (AIEgens) and iron oxide nanoparticles (IOs) to synergistically enhance near-infrared fluorescence (NIRF) intensity and magnetic resonance (MR) contrast through a tumor acidity-mediated click reaction. Tumor acidity-responsive IOs containing dibenzocyclooctyne groups (termed cDIOs) and AIEgens containing azide groups (termed AATs) can be covalently cross-linked in response to tumor acidity, which leads to a simultaneous enhancement in NIRF intensity (≈12.4-fold) and r 2 relaxivity (≈2.8-fold). cDIOs and AATs were effectively activated in mice orthotropic breast tumor, and the cross-linking prolonged their retention in tumor, further augmenting the bimodal signals and expanding imaging time frame. This facile strategy leverages the inherent properties of probes themselves and demonstrates promise in future translational studies., (© 2023 Wiley-VCH GmbH.)

The use of metal nanoparticles (NPs) conjugated with natural herbal molecules in biomedical applications has been growing. In this work, we synthesized Iron oxide NPs conjugated with thymol (Fe 3 O 4 @Glu-Thymol) and investigated their antibacterial and anticancer potentials. Physicochemical features of the NPs were studied by FT-IR, EDS-mapping, XRD, DLS, zeta potential, and electron microscopy. The antibacterial activity of the NPs against Pseudomonas aeruginosa and anticancer activity for breast cancer cells was investigated by broth microdilution and MTT and flow cytometry assays, respectively. The expression of apoptosis signaling genes in breast cancer cells that were treated with the NPs was studied by qPCR assay. The NPs were spherical, in a size range of 40-66 nm, without impurities, and with zeta potential and hydrodynamic size of - 23 mV and 185 nm, respectively. Moreover, the FT-IR and XRD assays confirmed the proper synthesis of Fe 3 O 4 and conjugation with thymol. The minimum inhibitory concentration of the NPs for P. aeruginosa strains was 64-128 µg/mL. Our results showed that Fe 3 O 4 @Glu-Thymol was considerably more toxic for breast cancer cells than normal human cells and the 50% inhibitory concentration were 90.4 and 322 µg/mL, respectively. Upon treating breast cancer cells with the NPs the frequency of cell apoptosis increased by 18.9%. Also, the expression of the BAX and CASP8 genes in NPs treated cells significantly increased by 1.75 and 2.25 folds, respectively while the BCL-2 gene remained almost constant. This study reveals that Fe 3 O 4 @Glu-Thymol has considerable potential to be used in biomedical fields., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Nanotechnology and material science have developed enormously fast in recent years. Due to their excellent magnetic properties, iron oxide nanoparticles (IONPs) have been broadly applied in the field of bioengineering and biomedical. Thus, it is important to evaluate the safety issues and health effects of these nanomaterials. The present investigation was aimed to evaluate the adverse effects of IONPs on human umbilical vein endothelial cells (HUVECs)., Methods: The cytotoxic potential of IONPs was assessed by MTT and neutral red uptake (NRU) assays. The impact of IONPs on oxidative stress markers (glutathione (GSH) and lipid peroxidation (LPO)), reactive oxygen species (ROS) production, and mitochondrial membrane potential (MMP) was also examined. Furthermore, the toxic effect of IONPs was quantified by assessing DNA damage, cell cycle arrest, and apoptosis by quantitative real time PCR., Results: We found that IONPs induce a dose-dependent cytotoxicity on HUVECs with IC 50 value of 79.13 μg/mL. The results also displayed that IONPs induce oxidative stress, ROS production, and mitochondrial membrane dysfunction. The comet assay results exhibited IONPs induces DNA damage in HUVECs. We found significant cell cycle arrest at SubG1 phase in treated cells and consequent cell death was evidenced by microscopic analysis. Moreover, IONPs display substantial up-regulation of pro-apoptotic genes and down-regulation of anti-apoptotic gene evidenced by real time qPCR., Conclusion: Overall, our results clearly demonstrated that IONPs have the potential to induce cytotoxicity, DNA damage, cell cycle arrest, and apoptosis in HUVECs mediated through oxidative stress and ROS production. Thus, IONPs are cytotoxic and it should be handled with proper care., 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 GmbH. All rights reserved.)

A lot of nanomaterials have been applied to various nano-biotechnological fields, such as contrast agents, drug or gene delivery systems, cosmetics, and so on. Despite the expanding usage of nanomaterials, concerns persist regarding their potential toxicity. To address this issue, many scientists have tried to develop biocompatible nanomaterials containing phytochemicals as a promising solution. In this study, we synthesized biocompatible nanomaterials by using gallic acid (GA), which is a phytochemical, and coating it onto the surface of iron oxide nanoparticles (IONPs). Importantly, the GA-modified iron oxide nanoparticles (GA-IONPs) were successfully prepared through environmentally friendly methods, avoiding the use of harmful reagents and extreme conditions. The presence of GA on the surface of IONPs improved their stability and bioactive properties. In addition, cell viability assays proved that GA-IONPs possessed excellent biocompatibility in human dermal papilla cells (HDPCs). Additionally, GA-IONPs showed antioxidant activity, which reduced intracellular reactive oxygen species (ROS) levels in an oxidative stress model induced by hydrogen peroxide (H 2 O 2 ). To investigate the impact of GA-IONPs on exosome secretions from oxidative stress-induced cells, we analyzed the number and characteristics of exosomes in the culture media of HDPCs after H 2 O 2 stimulation or GA-IONP treatment. Our analysis revealed that both the number and proportions of tetraspanins (CD9, CD81, and CD63) in exosomes were similar in the control group and the GA-IONP-treated groups. In contrast, exosome secretion was increased, and the proportion of tetraspanin was changed in the H 2 O 2 -treated group compared to the control group. It demonstrated that treatment with GA-IONPs effectively attenuated exosome secretion induced by H 2 O 2 -induced oxidative stress. Therefore, this GA-IONP exhibited outstanding promise for applications in the field of nanobiotechnology.

The present study is the first attempt to utilize the root extracts of Glycyrrhiza glabra as a novel biological route for the synthesis of iron oxide nanoparticles (Fe 2 O 3 NPs) under optimized conditions. The process variables namely concentration of ferric chloride, root extract of G. glabra and temperature were optimized using Response Surface Methodology (RSM) to obtain high yield. Phytochemicals mediated the reduction process and served as capping and stabilizing agent. The biosynthesized Fe 2 O 3 NPs characterized using UV-Vis spectroscopy exhibited a prominent peak at 350 nm. The crystallinity and valence state of Fe 2 O 3 NPs was confirmed by XRD and XPS. The surface functionalization of the nanoparticles was confirmed from the presence of functional groups in the FT-IR spectrum. The FESEM analysis revealed the biosynthesized Fe 2 O 3 NPs are irregular and the EDX spectrum recorded the presence of iron and oxygen in the synthesized nanoparticles. The biosynthesized Fe 2 O 3 NPs exhibited an appreciable photocatalytic activity against methylene blue under sunlight with a maximum decolorisation efficiency of 92% within 180 min of reaction time. The experimental data of adsorption studies well fitted with Langmuir isotherm and pseudo-second order kinetic model. The thermodynamic study proved to be spontaneous, feasible and endothermic in nature. The phytotoxicity study revealed 92% germination and increased seedling growth in the green gram seeds exposed to Fe 2 O 3 NPs. Hence the study established the efficiency of biosynthesized of Fe 2 O 3 NPs in photocatalytic and phytotoxic activities., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In this research, a multi-step microfluidic reactor was used to fabricate chitosan - superparamagnetic iron oxide composite nanoparticles (Ch - SPIONs), where composite formation using chitosan was aimed to provide antibacterial property and nanoparticle stability for magnetic resonance imaging (MRI). Monodispersed Ch - SPIONs had an average particle size of 8.8 ± 1.2 nm with a magnetization value of 32.0 emu/g. Ch - SPIONs could be used as an MRI contrast agent by shortening T 2 relaxation parameter of the surrounding environment, as measured on a 3 T MRI scanner. In addition, Ch - SPIONs with concentrations less than 1 g/L promoted bone cell (osteoblast) viability up to 7 days of culture in vitro in the presence of 0.4 T external static magnetic field. These nanoparticles were also tested against Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), which are dangerous pathogens that cause infection in tissues and biomedical devices. Upon interaction of Ch - SPIONs with S. aureus and P. aeruginosa at 0.01 g/L concentration, nearly a 2-fold reduction in the number of colonies was observed for both bacteria strains at 48 h of culture. Results cumulatively showed that Ch - SPIONs were potential candidates as a cytocompatible and antibacterial agent that can be targeted to biofilm and imaged using an MRI., (© 2023 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Cuprizone (CUP) induces neurotoxicity and demyelination in animal models by provoking the activation of glial cells and the generation of reactive oxygen species (ROS). Sulforaphane (SF) is a phytochemical that exhibits a neuroprotective potential. In this study, we investigated the neurotherapeutic and pro-remyelinating activities of SF and SF-loaded within iron oxide nanoparticles (IONP-SF) in CUP-exposed rats. Magnetite iron oxide nanoparticles (IONPs) were prepared using the hydrothermal method that was further loaded with SF (IONP-SF). The loading of SF within the magnetite nanoparticles was assessed using FTIR, TEM, DLS, Zetasizer, and XPS. For the in vivo investigations, adult male Wistar rats ( n  = 40) were administrated either on a regular diet or a diet with CUP (0.2%) for 5 weeks. The rats were divided into four groups: negative control, CUP-induced, CUP + SF, and CUP + IONP-SF. CUP-exposed brains exhibited a marked elevation in lipid peroxidation, along with a significant decrease in the activities of glutathione peroxidase (GPx), and catalase (CAT). In addition, CUP intoxication downregulated the expression of myelin basic protein (MBP) and myelin proteolipid protein (PLP), upregulated the expression of Matrix metallopeptidase-9 (MMP-9) and S100β, and increased caspase-3 immunoexpression, these results were supported histopathologically in the cerebral cortexes. Treatment of CUP-rats with either SF or IONP-SF demonstrated remyelinating and neurotherapeutic activities. We could conclude that IONP-SF was more effective than free SF in mitigating the CUP-induced downregulation of MBP, upregulation of S100β, and caspase-3 immunoexpression.

The iron nanoparticles (Fe-NPs) have been synthesized using an environmentally friendly and simple green synthesis method. This study aims to obtain an aqueous extract from natural material wastes for synthesizing Fe-NPs. The produced Fe-NPs were evaluated as adsorbents for removing Pb, Se, Cu, Zn, and Cr from aqueous solutions. The formation of Fe-NPs was observed on exposure of the aqueous extract to the ferrous chloride and ferric chloride solutions. The characterization of the synthesized Fe-NPs was carried out using different instrumental techniques. As a function of the initial metal ion concentration, contact time, and various doses, the removal of the heavy metal ions was investigated. The UV-Vis spectrum of Fe-NPs showed a peak at 386 nm, 386 nm, 400 nm, 420 nm, 210 nm, 215 nm, and 272 nm of banana, pomegranate, opuntia, orange, potato, and onion, respectively. The FT-IR spectra confirmed the attachment of bioactive molecules from plants on the Fe-NPs surface. The effective reduction of metal ions was greatly aided by the -OH functional groups. The functional groups were examined and responsible for adsorption process by nanoparticle powder sample, these peaks are 3400 cm-1, 2900 cm-1, 1600 cm-1,1000 cm-1, and 1550 cm-1. The magnetization measurements revealed superparamagnetic behavior in the produced iron oxide nanoparticles. Heavy metal ions uptake followed a time, dose, and initial concentration-dependent profile, with maximum removal efficiency at 45 min, 0.4 g, and 3.0 mg/L of metal concentration, respectively., Competing Interests: No conflicts of interest exist, according to the authors, with the publishing of this paper., (Copyright: © 2023 Al Shammari 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 potential of standard methods of radiation therapy is limited by the dose that can be safely delivered to the tumor, which could be too low for radical treatment. The dose efficiency can be increased by using radiosensitizers. In this study, we evaluated the sensitizing potential of biocompatible iron oxide nanoparticles coated with a dextran shell in A172 and Gl-Tr glioblastoma cells in vitro. The cells preincubated with nanoparticles for 24 h were exposed to ionizing radiation (X-ray, gamma, or proton) at doses of 0.5-6 Gy, and their viability was assessed by the Resazurin assay and by staining of the surviving cells with crystal violet. A statistically significant effect of radiosensitization by nanoparticles was observed in both cell lines when cells were exposed to 35 keV X-rays. A weak radiosensitizing effect was found only in the Gl-Tr line for the 1.2 MeV gamma irradiation and there was no radiosensitizing effect in both lines for the 200 MeV proton irradiation at the Bragg peak. A slight (ca. 10%) increase in the formation of additional reactive oxygen species after X-ray irradiation was found when nanoparticles were present. These results suggest that the nanoparticles absorbed by glioma cells can produce a significant radiosensitizing effect, probably due to the action of secondary electrons generated by the magnetite core, whereas the dextran shell of the nanoparticles used in these experiments appears to be rather stable under radiation exposure.

Iron oxide nanoparticles (IONPs) have great application potential due to their multifunctional excellence properties, leading to the possibility of their release into soil environments. IONPs exhibit different adsorption properties toward environmental pollutants (e.g., heavy metals and organic compounds), thus the adsorption performance for various contaminants and the molecular interactions at the IONPs-pollutants interface are discussed. After solute adsorption, the change in the environmental behavior of IONPs is an important transformation process in the natural environments. The aggregation, aging process, and chemical/biological transformation of IONPs can be altered by soil solution chemistry, as well as by the presence of dissolved organic matter and microorganisms. Upon exposure to soil environments, IONPs have both positive and negative impacts on soil organisms (e.g., bacteria, plants, nematodes, and earthworms). Moreover, we compared the toxicity of IONPs alone to combined toxicity with environmental pollutants and pristine IONPs to aged IONPs, and the mechanisms of IONPs toxicity at the cellular level are also reviewed. Given the unanswered questions, future research should include prediction and design of IONPs, new characterization technology for monitoring IONPs transformation in soil ecosystems, and further refinement the environmental risk assessment of IONPs. This review will greatly enhance our knowledge of the performance and impact of IONPs in soil 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 © 2023 Elsevier B.V. All rights reserved.)

Iron oxide nanoparticles (IONPs) are characterized by superior magnetic properties, high surface area to volume ratio, and active surface functional groups. These properties aid in removal of pollutants from water, through adsorption and/or photocatalysis, justifying the choice of IONPs in water treatment systems. IONPs are usually developed from commercial chemicals of ferric and ferrous salts alongside other reagents, a procedure that is costly, environmentally unfriendly and limits their mass production. On the other hand, steel and iron industries produce both solid and liquid wastes which in most cases are piled, discharged into water streams or landfilled as strategies to dispose them off. Such practices are detrimental to environmental ecosystems. Given the high content of iron present in these wastes, they can be used to generate IONPs. This work reviewed published literature through selected key words on the deployment of steel and/or iron-based wastes as IONPs precursors for water treatment. The findings reveal that steel waste-derived IONPs have properties such as specific surface area, particle sizes, saturation magnetization, and surface functional groups that are comparable or sometimes better than those synthesized from commercial salts. Furthermore, the steel waste-derived IONPs have high removal efficacy for heavy metals and dyes from water with possibilities of being regenerated. The performance of steel waste-derived IONPs can be enhanced by functionalization with different reagents such as chitosan, graphene, and biomass based activated carbons. Nonetheless, there is need to explore the potential of steel waste-based IONPs in removing contaminants of emerging concern, modifying pollutant detection sensors, their techno-economic feasibility in large treatment plants, toxicity of these nanoparticles when ingested into the human body, among other areas., 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.)

Nano-enabled agriculture has emerged as an attractive approach for facilitating soil pollution mitigation and enhancing crop production and nutrition. In this study, we conducted a greenhouse experiment to explore the efficacy of silicon oxide nanoparticles (SiONPs) and iron oxide nanoparticles (FeONPs) in alleviating arsenic (As) toxicity in wheat (Triticum aestivum L.) and elucidated the underlying mechanisms involved. The application of SiONPs and FeONPs at 25, 50, and 100 mg kg -1 soil concentration significantly reduced As toxicity and concurrently improved plant growth performance, including plant height, dry matter, spike length, and grain yield. The biochemical analysis showed that the enhanced plant growth was mainly due to stimulated antioxidative enzymes (catalase, superoxide dismutase, peroxidase) and reduced reactive oxygen species (electrolyte leakage, malondialdehyde, and hydrogen peroxide) in wheat seedlings under As stress upon NPs application. The nanoparticles (NPs) exposure also enhanced the photosynthesis efficiency, including the total chlorophyll and carotenoid contents as compared with the control treatment. Importantly, soil amendments with 100 mg kg -1 FeONPs significantly reduced the acropetal As translocation in the plant root, shoot and grains by 74%, 54% and 78%, respectively, as compared with the control treatment under As stress condition, with relatively lower reduction levels (i.e., 64%, 37% and 58% for the plant root, shoot and grains, respectively) for SiONPs amendment. Overall, the application of NPs especially the FeONPs as nanoferlizers for agricultural crops is a promising approach towards mitigating the negative impact of HMs toxicity, ensuring food safety, and promoting future sustainable agriculture., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Proton therapy allows the treatment of specific areas and avoids the surrounding tissues. However, this technique has uncertainties in terms of the distal dose fall-off. A promising approach to studying the proton range is the use of nanoparticles as proton-activatable agents that produce detectable signals. For this, we developed an iron oxide nanoparticle doped with Zn (IONP@Zn-cit) with a hydrodynamic size of 10 nm and stability in serum. Cytotoxicity, defined as half of the surveillance, was 100 μg Zn/mL in the U251 cell line. The effect on clonogenic cell death was tested after X-ray irradiation, which suggested a radioprotective effect of these nanoparticles at low concentrations (1-10 μg Zn/mL). To evaluate the production of positron emitters and prompt-gamma signals, IONP@Zn-cit was irradiated with protons, obtaining prompt-gamma signals at the lowest measured concentration (10 mg Zn/mL). Finally, 67 Ga-IONP@Zn-cit showed accumulation in the liver and spleen and an accumulation in the tumor tissue of 0.95% ID/g in a mouse model of U251 cells. These results suggest the possibility of using Zn nanoparticles as proton-activatable agents to verify the range by prompt gamma detection and face the challenges of prompt gamma detection in a specific biological situation, opening different avenues to go forward in this field.

To realize the accurate diagnosis of tumors by magnetic resonance imaging (MRI), switchable magnetic resonance contrast agents (CAs) between T 1 and T 2 contrast enhancement that are constructed based on extremely small iron oxide nanoparticles (ESIONPs) have been developed in recent years. We herein report, for the first time, a novel ESIONP-based nanocluster (named EAmP), which exhibited hypoxia responsiveness to the tumor microenvironment and offered a T 2 -to-T 1 -switchable contrast enhancement function, effectively distinguishing between the normal tissue and tumor tissue. In detail, active perfluorophenyl ester-modified ESIONPs with a diameter of approximately 3.6 nm were initially synthesized, and then 4,4'-azodianiline was used as a cross-linker to facilitate the formation of nanoclusters from ESIONPs through the reaction between the active ester and amine. Finally, poly(ethylene glycol) was further modified onto nanoclusters by utilizing the remaining active ester residues. The resulting EAmP demonstrated satisfactory colloidal stability and favorable biosafety and exhibited a desired T 2 -to-T 1 -switchable function, as evidenced by conversion from nanocluster to the dispersed state and a significant decrease in the r 2 / r 1 ratio from 14.86 to 1.61 when exposed to a mimical hypoxic environment in the solution. Moreover, EAmP could decompose into dispersed ESIONPs at the tumor region, resulting in a switch from T 2 to T 1 contrast enhancement. This T 2 -to-T 1 -switchable contrast agent offers high sensitivity and signal-to-noise ratio to realize the accurate diagnosis of tumors. In conclusion, hypoxia-responsive EAmP is a potential MRI nanoprobe for improving the diagnostic accuracy of solid tumors.

Integrating an NIR fluorescent probe with a magnetic resonance imaging (MRI) agent to harvest complementary imaging information is challenging. Here, we have designed water-soluble, biocompatible, noncytotoxic, bright-NIR-emitting, sugar-functionalized, mechanically interlocked molecules (MIMs)-capped superparamagnetic ultrasmall Fe 3 O 4 NPs for targeted multimodal imaging. Dual-functional stoppers containing an unsymmetrical NIR squaraine dye interlocked within a macrocycle to construct multifunctional MIMs are developed with enhanced NIR fluorescence efficiency and durability. One of the stoppers of the axle is composed of a lipophilic cationic TPP + functionality to target mitochondria, and the other stopper comprises a dopamine-containing catechol group to anchor at the surface of the synthesized Fe 3 O 4 NPs. Fe 3 O 4 NPs surface-coated with targeted NIR rotaxanes help to deliver ultrasmall magnetic NPs specifically inside the mitochondria. Two carbohydrate moieties are conjugated with the macrocycle of the rotaxane via click chemistry to improve the water solubility of MitoSQRot-(Carb-OH) 2 -DOPA-Fe 3 O 4 NPs. Water-soluble, rotaxane-capped Fe 3 O 4 NPs are used for live-cell mitochondria-targeted NIR fluorescence confocal imaging, 3D and multicolor imaging in combination with T 2 -weighted MRI on a 9.4 T MR scanner with a high relaxation rate ( r 2 ) of 180.7 mM -1 s -1 . Biocompatible, noncytotoxic, ultrabright NIR rotaxane-capped superparamagnetic ultrasmall monodisperse Fe 3 O 4 NPs could be a promising agent for targeted multimodal imaging applications.

Magnetic particle imaging (MPI) is a powerful and rapidly growing tomographic imaging technique that allows for the non-invasive visualization of superparamagnetic nanoparticles (NPs) in living matter. Despite its potential for a wide range of applications, the intrinsic quantitative nature of MPI has not been fully exploited in biological environments. In this study, a novel NP architecture that overcomes this limitation by maintaining a virtually unchanged effective relaxation (Brownian plus Néel) even when immobilized is presented. This superparamagnetic magnetite architecture made of phenolic resin hollow spheres coated with Eu(III) containing silica nanoparticles (SMART RHESINs) was synthesized and studied. Magnetic particle spectroscopy (MPS) measurements confirm their suitability for potential MPI applications. Photobleaching studies show an unexpected photodynamic due to the fluorescence emission peak of the europium ion in combination with the phenol formaldehyde resin (PFR). Cell metabolic activity and proliferation behavior are not affected. Colocalization experiments reveal the distinct accumulation of SMART RHESINs near the Golgi apparatus. Overall, SMART RHESINs show superparamagnetic behavior and special luminescent properties without acute cytotoxicity, making them suitable for bimodal imaging probes for medical use like cancer diagnosis and treatment. SMART RHESINs have the potential to enable quantitative MPS and MPI measurements both in mobile and immobilized environments., (© 2023 The Authors. Small published by Wiley-VCH GmbH.)

Background: Cancer cells are resistant to treatments such as chemotherapy and radiotherapy due to their characteristics such as self-renewal, high proliferation and other resistance mechanisms. To overcome this resistance, we combined a light-based treatment with nanoparticles to get advantage of both PDT and PTT in order to increase efficiency and beater outcome., Methods and Material: After synthesis and characterization of CoFe2O4@citric@PEG@ICG@ PpIX NPs, their dark cytotoxicity concentration was determined with MTT assay. Then light-base treatments were performed by two different light source for MDA-MB-231 and A375 cell lines. After treatment, the results were evaluated 48 h and 24 h after treatment by MTT assay and flow cytometry. Among CSCs defined markers, CD44, CD24 and CD133 are the most widely-used markers in CSC research and are also therapeutic targets in cancers. So we used proper antibodies to detect CSCs. Then indexes like ED50, synergism defined to evaluated the treatment., Results: ROS production and temperature increase have a direct relationship with exposure time. In both cell lines, the death rate in combinational treatment (PDT/PTT) is higher than single treatment and the amount of cells with CD44+CD24- and CD133+CD44+ markers has decreased. According to the synergism index, conjugated NPs show a high efficiency in use in light-based treatments. This index was higher in cell line MDA-MB-231 than A375. And the ED50 is proof of the high sensitivity of A375 cell line compared to MDA-MB-231 in PDT and PTT., Conclusion: Conjugated NPs along with combined photothermal and photodynamic therapies may play an important role in eradication CSCs., Competing Interests: Declaration of Competing Interest The authors have declared that no conflict interest exists., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Nanotechnology has been gaining more and more momentum lately and the potential use of nanomaterials such as nanoparticles (NPs) continues to grow in a variety of activity sectors. Among the NPs, iron oxide nanoparticles (IONs) have retained an increasing interest from the scientific community and industrials due to their superparamagnetic properties allowing their use in many fields, including medicine. However, some undesired effects of IONs and potential risk for human health are becoming increasingly reported in several studies. Although many in vivo studies reported that IONs induce immunotoxicity in different animal models, it is not clear how IONs can alter the biology of primary human immune cells. In this article, we will review the works that have been done regarding the interaction between IONs and primary immune cells. This review also outlines the importance of using primary immune cells in risk assessment of NPs as a reliable strategy for encouraging non-animal studies approaches, to determine risks that might affect the human immune system following different exposure scenarios. Taken all together, the reported observations help to get a more global picture on how IONs alter the human immune system especially the fact that inflammation, known to involve several immune cell types, is frequently reported as an undesired effect of IONs., 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 article., (Copyright © 2023. Published by Elsevier Ltd.)

Several reports have shown that pharmaceuticals and personal care products (PPCPs) have some negative effects on anaerobic digestion (AD), yet there are no convenient and efficient strategies for mitigating the adverse influences. The typical PPCPs of carbamazepine have a strong negative effect on lactic acid AD process. Therefore, in this work, novel lanthanum-iron oxide (LaFeO 3 ) nanoparticles (NPs) were used for adsorption and bioaugmentation to weak the negative effects of carbamazepine. The adsorption removal of carbamazepine increased from 0 to 44.30% as the dosage of LaFeO 3 NPs was increased from 0 to 200 mg/L, providing the necessary prerequisites for bioaugmentation. Adsorption reduced the probability of direct contact between carbamazepine and anaerobes, partly alleviating the inhibition of carbamazepine on microbes. The highest methane (CH 4 ) yield induced by LaFeO 3 NPs (25 mg/L) was 226.09 mL/g lactic acid, increasing by 30.06% compared to the control yield with a recovery to 89.09% of the normal CH 4 yield. Despite the ability of LaFeO 3 NPs to restore normal AD performance, the biodegradation rate of carbamazepine remained below 10% due to its anti-biodegradability. Bioaugmentation was primarily reflected in the enhanced bioavailability of dissolved organic matter, while the intracellular LaFeO 3 NPs promoted coenzyme F420 activity through binding to humic substances. Under the mediation of LaFeO 3 , a direct interspecies electron transfer system with Longilinea and Methanosaeta as functional bacteria was successfully constructed and the corresponding electron transfer rate was accelerated from 0.021 s -1 to 0.033 s -1 . LaFeO 3 NPs eventually recovered AD performance under carbamazepine stress in an adsorption and bioaugmentation manner., 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.)

Upon contact with biological fluids like serum, a protein corona (PC) complex forms on iron oxide nanoparticles (IONPs) in physiological environments and the proteins it contains influence how IONPs act in biological systems. Although the biological identity of PC-IONP complexes has often been studied in vitro and in vivo , there have been inconsistent results due to the differences in the animal of origin, the type of biological fluid, and the physicochemical properties of the IONPs. Here, we identified differences in the PC composition when it was derived from the sera of three species (bovine, murine, or human) and deposited on IONPs with similar core diameters but with different coatings [dimercaptosuccinic acid (DMSA), dextran (DEX), or 3-aminopropyl triethoxysilane (APS)], and we assessed how these differences influenced their effects on macrophages. We performed a comparative proteomic analysis to identify common proteins from the three sera that adsorb to each IONP coating and the 10 most strongly represented proteins in PCs. We demonstrated that the PC composition is dependent on the origin of the serum rather than the nature of the coating. The PC composition critically affects the interaction of IONPs with macrophages in self- or non-self identity models, influencing the activation and polarization of macrophages. However, such effects were more consistent for DMSA-IONPs. As such, a self biological identity of IONPs promotes the activation and M2 polarization of murine macrophages, while a non-self biological identity favors M1 polarization, producing larger quantities of ROS. In a human context, we observed the opposite effect, whereby a self biological identity of DMSA-IONPs promotes a mixed M1/M2 polarization with an increase in ROS production. Conversely, a non-self biological identity of IONPs provides nanoparticles with a stealthy character as no clear effects on human macrophages were evident. Thus, the biological identity of IONPs profoundly affects their interaction with macrophages, ultimately defining their biological impact on the immune system.

Coated iron oxide nanoparticles (IONs) are promising candidates for various applications in nanomedicine, including imaging, magnetic hyperthermia, and drug delivery. The application of IONs in nanomedicine is influenced by factors such as biocompatibility, surface properties, agglomeration, degradation behavior, and thrombogenicity. Therefore, it is essential to investigate the effects of coating material and thickness on the behavior and performance of IONs in the human body. In this study, IONs with a carboxymethyl dextran (CMD) coating and two thicknesses of silica coating (TEOS0.98, and TEOS3.91) were screened and compared to bare iron oxide nanoparticles (BIONs). All three coated particles showed good cytocompatibility (>70%) when tested with smooth muscle cells over three days. To investigate their potential long term behavior inside the human body, the Fe 2+ release and hydrodynamic diameters of silica-coated and CMD (carboxymethyl dextrane)-coated IONs were analyzed in simulated body fluids for 72 h at 37 °C. The ION@CMD showed moderate agglomeration of around 100 nm in all four simulated fluids and dissolved faster than the silica-coated particles in artificial exosomal fluid and artificial lysosomal fluid. The particles with silica coating agglomerated in all tested simulated media above 1000 nm. Increased thickness of the silica coating led to decreased degradation of particles. Additionally, CMD coating resulted in nanoparticles with the least prothrombotic activity, and the thick silica coating apparently decreased the prothrombotic properties of nanoparticles compared to BIONs and ION@TEOS0.98. For magnetic resonance applications, ION@CMD and ION@TEOS3.91 showed comparatively high relaxation rates R 2 values. In magnetic particle imaging experiments ION@TEOS3.91 yielded the highest normalized signal to noise ratio values and in magnetic hyperthermia studies, ION@CMD and ION@TEOS0.98 showed similar specific loss power. These findings demonstrate the potential of coated IONs in nanomedicine and emphasize the importance of understanding the effect of coating material and thickness on their behavior and performance in the human body., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Magnetic iron oxide nanoparticles (magnetite and maghemite) are intensively studied due to their broad potential applications in medical and biological sciences. Their unique properties, such as nanometric size, large specific surface area, and superparamagnetism, allow them to be used in targeted drug delivery and internal radiotherapy by targeting an external magnetic field. In addition, they are successfully used in magnetic resonance imaging (MRI), hyperthermia, and radiolabelling. The appropriate design of nanoparticles allows them to be delivered to the desired tissues and organs. The desired biodistribution of nanoparticles, eg, cancerous tumors, is increased using an external magnetic field. Thus, knowledge of the biodistribution of these nanoparticles is essential for medical applications. It allows for determining whether nanoparticles are captured by the desired organs or accumulated in other tissues, which may lead to potential toxicity. This review article presents the main organs where nanoparticles accumulate. The sites of their first uptake are usually the liver, spleen, and lymph nodes, but with the appropriate design of nanoparticles, they can also be accumulated in organs such as the lungs, heart, or brain. In addition, the review describes the factors affecting the biodistribution of nanoparticles, including their size, shape, surface charge, coating molecules, and route of administration. Modern techniques for determining nanoparticle accumulation sites and concentration in isolated tissues or the body in vivo are also presented., Competing Interests: The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Nowak-Jary and Machnicka.)

We have investigated the efficacy of superparamagnetic iron oxide nanoparticles (SPIONs) as positive T 1 contrast agents for low-field magnetic resonance imaging (MRI) at 64 millitesla (mT). Iron oxide-based agents, such as the FDA-approved ferumoxytol, were measured using a variety of techniques to evaluate T 1 contrast at 64 mT. Additionally, we characterized monodispersed carboxylic acid-coated SPIONs with a range of diameters (4.9-15.7 nm) in order to understand size-dependent properties of T 1 contrast at low-field. MRI contrast properties were measured using 64 mT MRI, magnetometry, and nuclear magnetic resonance dispersion (NMRD). We also measured MRI contrast at 3 T to provide comparison to a standard clinical field strength. SPIONs have the capacity to perform well as T 1 contrast agents at 64 mT, with measured longitudinal relaxivity (r 1 ) values of up to 67 L mmol -1  s -1 , more than an order of magnitude higher than corresponding r 1 values at 3 T. The particles exhibit size-dependent longitudinal relaxivities and outperform a commercial Gd-based agent (gadobenate dimeglumine) by more than eight-fold at physiological temperatures. Additionally, we characterize the ratio of transverse to longitudinal relaxivity, r 2 /r 1 and find that it is ~ 1 for the SPION based agents at 64 mT, indicating a favorable balance of relaxivities for T 1 -weighted contrast imaging. We also correlate the magnetic and structural properties of the particles with models of nanoparticle relaxivity to understand generation of T 1 contrast. These experiments show that SPIONs, at low fields being targeted for point-of-care low-field MRI systems, have a unique combination of magnetic and structural properties that produce large T 1 relaxivities., (© 2023. The Author(s).)

Exerting forces on biomolecules inside living cells would allow us to probe their dynamic interactions in their native environment. Magnetic iron oxide nanoparticles represent a unique tool capable of pulling on biomolecules with the application of an external magnetic field gradient; however, their use has been restricted to biomolecules accessible from the extracellular medium. Targeting intracellular biomolecules represents an additional challenge due to potential nonspecific interactions with cytoplasmic or nuclear components. We present the synthesis of sulfobetaine-phosphonate block copolymer ligands, which provide magnetic nanoparticles that are stealthy and targetable in living cells. We demonstrate, for the first time, their efficient targeting in the nucleus and their use for magnetic micromanipulation of a specific genomic locus in living cells. We believe that these stable and sensitive magnetic nanoprobes represent a promising tool to manipulate specific biomolecules in living cells and probe the mechanical properties of living matter at the molecular scale.

The therapeutic efficacy and adverse impacts of nanoparticles (NPs) are strongly dependent on their systemic circulation time. The corona proteins adsorbed on the NPs determine their plasma half-lives, and hence, it is crucial to identify the proteins shortening or extending their circulation time. In this work, the in vivo circulation time and corona composition of superparamagnetic iron oxide nanoparticles (SPIONs) with different surface charges/chemistries were analyzed over time. SPIONs with neutral and positive charges showed the longest and shortest circulation times, respectively. The most striking observation was that corona-coated NPs with similar opsonin/dysopsonin content showed different circulation times, implying these biomolecules are not the only contributing factors. Long-circulating NPs adsorb higher concentrations of osteopontin, lipoprotein lipase, coagulation factor VII, matrix Gla protein, secreted phosphoprotein 24, alpha-2-HS-glycoprotein, and apolipoprotein C-I, while short-circulating NPs adsorb higher amounts of hemoglobin. Therefore, these proteins may be considered to be determining factors governing the NP systemic circulation time.

Magnetic nanoparticles (MNPs) have gained significant attention among several nanoscale materials during the last decade due to their unique properties. These properties make them successful nanofillers for drug delivery and a number of new biomedical applications. MNPs are more useful when combined with biodegradable polymers. In this review, we discussed the synthesis of polycaprolactones (PCL) and the various methods of synthesizing magnetic iron oxide nanoparticles. Then, the synthesis of composites that is made of PCL and magnetic materials (with special focus on iron oxide nanoparticles) were highlighted. In addition, we comprehensively reviewed their application in drug delivery, cancer treatment, wound healing, hyperthermia, and bone tissue engineering. Other biomedical applications of the magnetic PCL such as mitochondria targeting are highlighted. Moreover, biomedical applications of magnetic nanoparticles incorporated into other synthetic polymers apart from PCL are also discussed. Thus, great progress and better outcome with functionalized MNPs enhanced with polycaprolactone has been recorded with the biomedical applications of drug delivery and recovery of bone tissues., 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 B.V. All rights reserved.)

Iron oxide nanoparticles (IONPs) are advanced materials for water remediation technologies. It is therefore relevant to evaluate the cellular and tissue behavior of fishes in response to IONPs and their associations with agrochemicals such as glyphosate (GLY) and glyphosate-based herbicides (GBHs). Iron accumulation, tissue integrity and lipid distribution in the hepatocytes of Poecilia reticulata (guppy) were investigated in a control group and in groups exposed to soluble iron ions, namely IFe (0.3 mgFe/L), IONPs (0.3 mgFe/L), and IONPs, associated with GLY (0.65 mg/L), GBHs 0.65 mgGLY/L (IONPs + GBH1), and 1.30 mgGLY/L (IONPs + GBH2), for 7, 14, and 21 days, followed by an equal period of postexposure in clean reconstituted water. The results showed that the accumulation of iron was greater in the subjects in the IONP treatment group when compared to that in the Ife group. In addition, the subjects in the mixtures with GBHs had a greater accumulation of iron than those in the IONP + GLY treatment group. Tissue integrity assessments demonstrated an intense accumulation of lipids, formation of necrotic zones and leukocyte infiltrates in all the treated groups, with a greater quantity of lipids in the animals treated with IONP + GLY and IFe. During postexposure, the results indicated an elimination of iron in all treated groups, reaching the same level as the control group, throughout the 21 days postexposure. Thus, the damage caused to animal livers by IONP mixtures is reversible, providing promising results for the development of safe environmental remediation practices using nanoparticles., 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.)

For the potential in vitro/in vivo applications of magnetic iron oxide nanoparticles, their stability in different physiological fluids has to be ensured. This important prerequisite includes the preservation of the particles' stability during the envisaged application and, consequently, their invariance with respect to the transfer from storage conditions to cell culture media or even bodily fluids. Here, we investigate the colloidal stabilities of commercial nanoparticles with different coatings as a model system for biogenic iron oxide nanoparticles (magnetosomes) isolated from magnetotactic bacteria. We demonstrate that the stability can be evaluated and quantified by determining the intensity-weighted average of the particle sizes ( Z -value) obtained from dynamic light scattering experiments as a simple quality criterion, which can also be used as an indicator for protein corona formation.

Iron oxide nanoparticles (IONPs) have been studied extensively for biomedical applications, which require that they be aqueous-stable at physiological pH. The structures of some of these buffers, however, may also allow for binding to surface iron, thus potentially exchanging with functionally relevant ligands, and altering the desired properties of the nanoparticles. We report here on the interactions of five common biologically relevant buffers (MES, MOPS, phosphate, HEPES, and Tris) with iron oxide nanoparticles through spectroscopic studies. The IONPs in this study are capped with 3,4-dihydroxybenzoic acid (3,4-DHBA) to serve as models for IONP functionalized with catechol ligands. Unlike previous studies, which relied exclusively on dynamic light scattering (DLS) and ζ-potential measurements to characterize buffer interactions with IONPs, we use Fourier transform infrared (FTIR) and ultraviolet-visible (UV-visible) spectroscopic techniques to characterize the IONP surface to demonstrate binding of buffers and etching of the IONP surface. Our findings establish that phosphate and Tris bind to the IONP surface, even in the presence of strongly bound catechol ligands. We further observe significant etching of IONPs in Tris buffer, with the release of surface Fe into solution. Minor etching is noted in HEPES, and to a lesser degree, in MOPS, while no etching is observed in MES. Our findings suggest that, while morpholino buffers, such as MES and MOPS, may be more appropriate for use with IONPs, proper buffer selection should always be considered on a case-by-case basis.

Type I interferons, particularly IFNα-2b, play essential roles in eliciting adaptive and innate immune responses, being implicated in the pathogenesis of various diseases, including cancer, and autoimmune and infectious diseases. Therefore, the development of a highly sensitive platform for analysis of either IFNα-2b or anti-IFNα-2b antibodies is of high importance to improve the diagnosis of various pathologies associated with the IFNα-2b disbalance. For evaluation of the anti-IFNα-2b antibody level, we have synthesized superparamagnetic iron oxide nanoparticles (SPIONs) coupled with the recombinant human IFNα-2b protein (SPIONs@IFNα-2b). Employing a magnetic relaxation switching assay (MRSw)-based nanosensor, we detected picomolar concentrations (0.36 pg/mL) of anti-INFα-2b antibodies. The high sensitivity of the real-time antibodies' detection was ensured by the specificity of immune responses and the maintenance of resonance conditions for water spins by choosing a high-frequency filling of short radio-frequency pulses of the generator. The formation of a complex of the SPIONs@IFNα-2b nanoparticles with the anti-INFα-2b antibodies led to a cascade process of the formation of nanoparticle clusters, which was further enhanced by exposure to a strong (7.1 T) homogenous magnetic field. Obtained magnetic conjugates exhibited high negative MR contrast-enhancing properties (as shown by NMR studies) that were also preserved when particles were administered in vivo. Thus, we observed a 1.2-fold decrease of the T2 relaxation time in the liver following administration of magnetic conjugates as compared to the control. In conclusion, the developed MRSw assay based on SPIONs@IFNα-2b nanoparticles represents an alternative immunological probe for the estimation of anti-IFNα-2b antibodies that could be further employed in clinical studies.

Nanotechnology is capturing great interest worldwide due to their stirring applications in various fields and also individual application of iron oxide nanoparticle (FeO-NPs) and zinc oxide nanoparticle (ZnO-NPs) have been studied in many literatures. However, the combined application of FeO and ZnO-NPs is a novel approach and studied in only few studies. For this purpose, a pot experiment was conducted to examine the plant growth and biomass, photosynthetic pigments, gas exchange attributes, oxidative stress and response of antioxidant compounds (enzymatic and nonenzymatic), sugars, nutritional status of the plant, organic acid exudation pattern As accumulation from the different parts of the plants in spinach (Spinacia oleracea L.) under the different As concentrations i.e., 0 (no As), 60 and 120 μM] which were primed with combined application of two levels of FeO-NPs (10 and 20 mg L -1 ) and ZnO-NPs (20 and 40 mg L -1 ). Results from the present study showed that the increasing levels of As in the soil significantly (P < 0.05) decreased plant growth and biomass, photosynthetic pigments, gas exchange attributes, sugars, and nutritional contents from the roots and shoots of the plants. In contrast, increasing levels of As in the soil significantly (P < 0.05) increased oxidative stress indicators in term of malondialdehyde, hydrogen peroxide, and electrolyte leakage, and also increased organic acid exudation patter in the roots of S. oleracea. The negative impact of As toxicity can overcome the combined application of ZnO-NPs and FeO-NPs, which ultimately increased plant growth and biomass by capturing the reactive oxygen species, and decreased oxidative stress in S. oleracea by decreasing the As contents in the roots and shoots of the plants. Research findings, therefore, suggest that the combined application of ZnO-NPs and FeO-NPs can ameliorate As toxicity in S. oleracea, resulting in improved plant growth and composition under As stress, as depicted by balanced exudation of organic acids., 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 Masson SAS. All rights reserved.)

Humans are exposed to a wide variety of natural and engineered nanoparticles (NPs) during their lifetime. However, the effects of pre-exposure to NPs on subsequent uptake of other NPs have not been investigated. In the present study, we investigated the effects of pre-exposure to three NPs (TiO 2 , Fe 2 O 3 , and SiO 2 NPs) on the subsequent uptake of gold NPs (AuNPs) by hepatocellular carcinoma cells (HepG2). When HepG2 cells were pre-exposed to TiO 2 or Fe 2 O 3 NPs, but not SiO 2 NPs for 2 days, their subsequent uptake of AuNPs was inhibited. Such inhibition was also observed in human cervical cancer (HeLa) cells, suggesting that this phenomenon is present in different cell types. The mechanisms underlying the inhibitory effect of NP pre-exposure include altered plasma membrane fluidity due to changes in lipid metabolism and reduced intracellular ATP production due to decreased intracellular oxygen. Despite the inhibitory effects of NP pre-exposure, full recovery was observed after transferring the cells to medium without NPs, even when the pre-exposure time was extended from 2 days to 2 weeks. Overall, the pre-exposure effects observed in the present study should be considered in the biological application and risk evaluation of NPs., 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 B.V. All rights reserved.)

Central nervous system (CNS) disorders affect as many as 1.5 billion people globally. The limited delivery of most imaging and therapeutic agents into the brain is a major challenge for treatment of CNS disorders. With the advent of nanotechnologies, controlled delivery of drugs with nanoparticles holds great promise in CNS disorders for overcoming the blood-brain barrier (BBB) and improving delivery efficacy. In recent years, magnetic iron oxide nanoparticles (MIONPs) have stood out as a promising theranostic nanoplatform for brain imaging and drug delivery as they possess unique physical properties and biodegradable characteristics. In this review, we summarize the recent advances in MIONP-based platforms as imaging and drug delivery agents for brain diseases. We firstly introduce the methods of synthesis and surface functionalization of MIONPs with emphasis on the inclusion of biocompatible polymers that allow for the addition of tailored physicochemical properties. We then discuss the recent advances in in vivo imaging and drug delivery applications using MIONPs. Finally, we present a perspective on the remaining challenges and possible future directions for MIONP-based brain delivery 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 © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

SNIO-CBP, a single-nanometer iron oxide (SNIO) nanoparticle functionalized with a type I collagen-binding peptide (CBP), was developed as a T -weighted MRI contrast agent with only endogenous elements for fast and noninvasive detection of liver fibrosis. SNIO-CBP exhibits 6.7-fold higher relaxivity compared to a molecular gadolinium-based collagen-binding contrast agent CM-101 on a per CBP basis at 4.7 T. Unlike most iron oxide nanoparticles, SNIO-CBP exhibits fast elimination from the bloodstream with a 5.7 min half-life, high renal clearance, and low, transient liver enhancement in healthy mice. We show that a dose of SNIO-CBP that is 2.5-fold lower than that for CM-101 has comparable imaging efficacy in rapid (within 15 min following intravenous injection) detection of hepatotoxin-induced liver fibrosis using 1 -weighted MRI contrast agent with only endogenous elements for fast and noninvasive detection of liver fibrosis. SNIO-CBP exhibits 6.7-fold higher relaxivity compared to a molecular gadolinium-based collagen-binding contrast agent CM-101 on a per CBP basis at 4.7 T. Unlike most iron oxide nanoparticles, SNIO-CBP exhibits fast elimination from the bloodstream with a 5.7 min half-life, high renal clearance, and low, transient liver enhancement in healthy mice. We show that a dose of SNIO-CBP that is 2.5-fold lower than that for CM-101 has comparable imaging efficacy in rapid (within 15 min following intravenous injection) detection of hepatotoxin-induced liver fibrosis using T 1 -weighted MRI in a carbon tetrachloride-induced mouse liver injury model. We further demonstrate the applicability of SNIO-CBP in detecting liver fibrosis in choline-deficient L -amino acid-defined high-fat diet mouse model of nonalcoholic steatohepatitis. These results provide a platform with potential for the development of high relaxivity, gadolinium-free molecular MRI probes for characterizing chronic liver disease.