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Integrating hyperthermia with conventional cancer therapies shows promise in improving treatment efficacy while mitigating their side effects. Nanotechnology-based hyperthermia, particularly using superparamagnetic iron oxide nanoparticles (SPIONs), offers a simplified solution for cancer treatment. In this study, we developed composites of SPION quantum dots (Fe3O4) with reduced graphene oxide (Fe3O4/RGO) using the coprecipitation method and investigated their potential application in magnetic hyperthermia. The size of Fe3O4 nanoparticles was controlled within the quantum dot range (≤10 nm) by varying the synthesis parameters, including reaction time as well as the concentration of ammonia and graphene oxide, where their biocompatibility was further improved with the inclusion of polyethylene glycol (PEG). These nanocomposites exhibited low cytotoxic effects on healthy cells (CHO-K1) over an incubation period of 24 h, though the inclusion of PEG enhanced their biocompatibility for longer incubation periods over 48 h. The Fe3O4/RGO composites dispersed in acidic pH buffer (pH 4.66) exhibited considerable heating effects, with the solution temperature increasing by ~10 °C within 5 min of exposure to pulsed magnetic fields, as compared to their dispersions in phosphate buffer and aqueous dimethylsulfoxide solutions. These results demonstrated the feasibility of using quantum dot Fe3O4/RGO composites for magnetic hyperthermia-based therapy to treat cancer, with further studies required to systematically optimize their magnetic properties and evaluate their efficacy for in vitro and in vivo applications. [ABSTRACT FROM AUTHOR]

Oral cancer is a worldwide health issue with high incidence and mortality, demands an effective treatment to improve patient prognosis. Superparamagnetic iron oxide nanoparticles (SPIONs) emerged as a candidate for oral cancer treatment due to their unique attributes, enabling a synergistic combination with its drug-delivery capabilities and hyperthermia when exposed to magnetic fields. SPIONs can be synthesized using biopolymers from agricultural waste like lignin from paddy, which produce biogenic nano iron oxide with superparamagnetic and antioxidant effects. In addition, lignin also acts as a stabilizing agent in creating SPIONs. This study aimed to explore how agricultural waste could be used to prepare SPIONs using the green synthesis method and to evaluate its potential for oral cancer specifically focusing on its effectiveness, side effects, biocompatibility, and toxicity. A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. PubMed, EBSCO, and Scopus databases were exploited in the selection of articles published within the last decade. This study quality assessment uses OHAT for critical appraisal tools. Only 10 studies met the inclusion criteria. The findings suggest that the use of agricultural waste in the preparation of SPIONs not only holds potency for oral cancer treatment through drug delivery and hyperthermia but also aligns with the concept of green dentistry. SPIONs as a treatment modality for oral cancer have demonstrated notable effectiveness and versatility. This study provides robust evidence supporting green dentistry by using agricultural waste in the preparation and formulation of SPIONs for managing oral cancer. Its multifunctional nature and ability to enhance treatment efficacy while minimizing adverse effects on healthy tissues highlights the potency of SPION-based oral cancer treatments. [ABSTRACT FROM AUTHOR]

Héctor M Ramos-Zaldívar,1 Iva Polakovicova2,3 ,† Edison Salas-Huenuleo,4 Claudia P Yefi,5 David Silva-Ancahuail,2,6 Pedro Jara-Guajardo,2,6 Juan Esteban Oyarzún,7,8 Álvaro Neira-Troncoso,3,9 Patricia V Burgos,9 Viviana A Cavieres,9 Eloísa Arias-Muñoz,9 Carlos Martínez,10 Ana L Riveros,2,6 Alejandro H Corvalán,2,3 Marcelo J Kogan,2,6 Marcelo E Andia7,8 1Doctoral Program in Medical Sciences, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; 2Advanced Center for Chronic Diseases (ACCDiS), Santiago, Chile; 3Department of Hematology and Oncology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; 4Advanced Integrated Technologies SpA, (AINTECH), Santiago, Chile; 5Escuela de Medicina Veterinaria, Facultad de Ciencias de la Naturaleza, Universidad San Sebastián, Santiago, Chile; 6Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Laboratorio de Nanobiotecnología, Universidad de Chile, Santiago, Chile; 7Millennium Institute for Intelligent Healthcare Engineering, Santiago, Chile; 8Biomedical Imaging Center, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile; 9Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Chile; 10Experimental Surgery and Simulation Center, Department of Digestive Surgery, Clinic Hospital, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile†Iva Polakovicova passed away on October 12, 2020Correspondence: Héctor M Ramos-Zaldívar, Email hmramos@uc.clIntroduction: The meningeal lymphatic vessels have been described as a pathway that transports cerebrospinal fluid and interstitial fluid in a unidirectional manner towards the deep cervical lymph nodes. However, these vessels exhibit anatomical and molecular characteristics typical of initial lymphatic vessels, with the absence of surrounding smooth muscle and few or absent valves. Given its structure, this network could theoretically allow for bidirectional motion. Nevertheless, it has not been assessed as a potential route for nanoparticles to travel from peripheral tissues to the brain.Methods: We employed superparamagnetic iron oxide nanoparticles (SPIONs), exosomes loaded with SPIONs, gold nanorods, and Chinese ink nanoparticles. SPIONs were prepared via chemical coprecipitation, while exosomes were isolated from the B16F10 melanoma cell line through the Exo-Spin column protocol and loaded with SPIONs through electroporation. Gold nanorods were functionalized with polyethylene glycol. We utilized C57BL/6 mice for post-mortem and in vivo procedures. To evaluate the retrograde directional flow, we injected each nanoparticle solution in the deep cervical lymph node. The head and neck were fixed for magnetic resonance imaging and histological analysis.Results: Here we show that extracellular vesicles derived from the B16F10 melanoma cell line, along with superparamagnetic iron oxide nanoparticles, gold nanorods, and Chinese ink nanoparticles can reach the meningeal lymphatic vessels and the brain of C57BL/6 mice after administration within the deep cervical lymph nodes post-mortem and in vivo, exclusively through lymphatic structures.Discussion: The functional anatomy of dural lymphatics has been found to be conserved between mice and humans, suggesting that our findings may have significant implications for advancing targeted drug delivery systems using nanoparticles. Understanding the retrograde transport of nanoparticles through the meningeal lymphatic network could lead to novel therapeutic approaches in nanomedicine, offering new insights into fluid dynamics in both physiological and neuropathological contexts. Further research into this pathway may unlock new strategies for treating neurological diseases or enhancing drug delivery to the brain.Keywords: extracellular vesicles, SPIONs, gold nanorods, Chinese ink, meningeal lymphatic vessels, nanomedicine

Endothelin-1/endothelin A receptor (ET-1/ETAR) pathway plays an important role in the progression of liver fibrosis by activating hepatic stellate cells (HSCs) - a key cell type involved in the pathogenesis of liver fibrosis. Inactivating HSCs by blocking the ET-1/ETAR pathway using a selective ETAR antagonist (ERA) represents a promising therapeutic approach for liver fibrosis. Unfortunately, small-molecule ERAs possess limited clinical potential due to poor bioavailability, short half-life, and rapid renal clearance. To improve the clinical applicability, we conjugated ERA to superparamagnetic iron-oxide nanoparticles (SPIONs) and investigated the therapeutic efficacy of ERA and ERA-SPIONs in vitro and in vivo and analyzed liver uptake by in vivo and ex vivo magnetic resonance imaging (MRI), HSCs-specific localization, and ET-1/ETAR-pathway antagonism in vivo. In murine and human liver fibrosis/cirrhosis, we observed overexpression of ET-1 and ETAR that correlated with HSC activation, and HSC-specific localization of ETAR. ERA and successfully synthesized ERA-SPIONs demonstrated significant attenuation in TGFβ-induced HSC activation, ECM production, migration, and contractility. In an acute CCl4-induced liver fibrosis mouse model, ERA-SPIONs exhibited higher liver uptake, HSC-specific localization, and ET-1/ETAR pathway antagonism. This resulted in significantly reduced liver-to-body weight ratio, plasma ALT levels, and α-SMA and collagen-I expression, indicating attenuation of liver fibrosis. In conclusion, our study demonstrates that the delivery of ERA using SPIONs enhances the therapeutic efficacy of ERA in vivo. This approach holds promise as a theranostic strategy for the MRI-based diagnosis and treatment of liver fibrosis.

The detection of magnetic nanoparticles in a liquid medium and the quantification of their concentration have the potential to improve the efficiency of several relevant applications in different fields, including medicine, environmental remediation, and mechanical engineering. To this end, sensors based on the magneto-impedance effect have attracted much attention due to their high sensitivity to the stray magnetic field generated by magnetic nanoparticles, their simple fabrication process, and their relatively low cost. To improve the sensitivity of these sensors, a multidisciplinary approach is required to study a wide range of soft magnetic materials as sensing elements and to customize the magnetic properties of nanoparticles. The combination of magneto-impedance sensors with ad hoc microfluidic systems favors the design of integrated portable devices with high specificity towards magnetic ferrofluids, allowing the use of very small sample volumes and making measurements faster and more reliable. In this work, a magneto-impedance sensor based on an amorphous Fe73.5Nb3Cu1Si13.5B9 wire as the sensing element is integrated into a customized millifluidic chip. The sensor detects the presence of magnetic nanoparticles in the ferrofluid and distinguishes the different stray fields generated by single-domain superparamagnetic iron oxide nanoparticles or magnetically blocked Co-ferrite nanoparticles. [ABSTRACT FROM AUTHOR]

The current work aims to investigate if the fibres extracted from the seeds of Coriandrum sativum and Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) coated fibres can be used as a low-cost bio-sorbent for the removal of dyes, antibiotics, and heavy metal from the aqueous medium. Moisture content, ash content, hemicellulose, cellulose, and lignin in the fibre have been determined, and the other characteristics were studied using Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, Zeta Potential analysis, and X-ray Diffraction analysis. The seeds and their fibres were coated with Superparamagnetic Iron Oxide Nanoparticles (SPIONs), and characterization studies were carried out. Different adsorbents were discovered to effectively remove various adsorbates under ideal circumstances which were optimized. The removal of anionic and cationic dyes, heavy metal, and antibiotics via the process of adsorption by the extracted fibres and SPION-coated Coriandrum sativum fibres has been explored along with different isotherm models. [ABSTRACT FROM AUTHOR]

Superparamagnetic iron oxide nanoparticles (SPIONs) possess intrinsic properties to serve as T2 contrast agents for magnetic resonance imaging (MRI) — a highly sensitive, non-invasive diagnostic tool. In this study, we have evaluated the potential of SPIONs by surface modifying it with generation 4 polyamidoamine dendrimers (G4 PAMAM). SPIONs were characterized using DLS, TEM, FTIR, VSM, and XRD. The dendrimer-coated SPIONs (DC-SPIONs) were characterized using NMR, FTIR, VSM, and XRD and their efficacy was studied using a 3 T clinical MR imager. SPIONs, DC-SPIONs, and dendrimers exhibit significant T2 contrast-enhancing properties while potentially improving interaction with cells. It was concluded that although SPIONs alone exhibit the highest contrast efficacy, the coating with dendrimers improvises their biocompatibility and dispersion in in vitro cells at clinically relevant concentrations ranging from 0.005 to 0.05 mmol/L−1. As expected, concentrations of 0.05 mmol/L−1 exhibited higher contrast-enhancing properties as compared to 0.005 mmol/L−1 but even at ultra-low concentrations, all materials exhibited qualitative and quantitative detection. [ABSTRACT FROM AUTHOR]

miRNAs (miRs) are short, noncoding RNA sequences that are present in biofluids such as blood, plasma, and serum. Their disrupted levels of expression correlate with different stages of various diseases, making them suitable as potential biomarkers. In this study, we present magnetic nanoprobes (MNPs) designed to capture specific target miRs (TmiRs) in biofluids like serum. The nanoprobes were formulated starting from PEGylated SPIONs using streptavidin–biotin interactions. The PEG chains were functionalized with complementary DNA sequence (cDNA-484) able to bind to TmiR-484, which is known to be overexpressed in serum of patients with colorectal cancer. The two-step formulation of the MNPs was monitored by SE-HPLC, following a previously established protocol. The colloidal stability of the MNPs and their ability to capture TmiR-484 were first determined in model solutions and then in human serum enriched with the commercially purchased TmiR-484. After magnetic sorting, the TmiR was released from the MNPs (dehybridization step) and quantified using qRT-PCR. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a multifactorial, heterogeneous systemic disease that is considered one of the leading causes of death and morbidity worldwide. It is well-known that endothelial dysfunction (ED) plays an important role in cardiac disease etiology. A reduction in the bioavailability of nitric oxide (NO) in the bloodstream leads to vasoconstriction and ED. Many studies indicated diminishment of peripheral arteries vasodilation that is mediated by the endothelium in the of patients with chronic HF. With the advancement of nanomedicine, nanotechnology can provide adequate solutions for delivering exogenous NO with the aid of nanoparticles (NPs) to treat ED. The properties of superparamagnetic iron oxide nanoparticles (SPIONs) enable both passive and active delivery of drugs. This prompted us to investigate the efficacy of our newly-developed hydrogel nanoparticles (NO-RPs) for the delivery and sustained release of NO gas to alleviate cardiac failure and inflammation in the heart failure zebrafish model. The hydrogel NO-RPs incorporate SPIONS and NO precursor. The sustainend release of NO in the NO-RPs (4200 s), overcomes the problem of the short half life of NO in vivo which is expected to ameliorate the reduced NO bioavailabilty, and its consequences in endothelial and cardiac dysfunction. Zebrafish embryos were used as the animal model in this study to determine the effect of SPIONs-loaded NO-RPs on the cardiovascular system. Cardiac failure was induced in 24hpf embryos by exposure to aristolochic acid (AA)(0.25, 0.5 μM) for 8 h, followed by the SPIONs-loaded NO-RPs (0.25, 0.5 mg/ml) for 48 h, experimental groups included: control group which is healthy non treated zebrafish embryos, AA injured zebrafish embryos (HF) model,and NO-RP treated HF zebrafish embryos. Survival rate was assessed at 72hpf. Cardiac function was also evaluated by analyzing cardiac parameters including heartbeat, major blood vessels primordial cardinal vein and dorsal aorta (PCV &DA) diameter, blood flow velocity in PCV & DA vessels, cardiac output, and PCV & DA shear stresses. All cardiac parameters were analyzed with the aid of MicroZebraLab blood flow analysis software from Viewpoint. In addition, we studied the molecular effects of the developed NO-RPs on the mRNA expression of selected pro-inflammatory markers: IL-6, and Cox-2. Our findings demonstrated that the NO-RPs improved the survival rate in the heart failure zebrafish model and reversed heart failure by enhancing blood flow perfusion in Zebrafish embryos, significantly. In addition, RT-PCR results showed that the NO-RPs significantly reduced the expression of pro-inflammatory markers (lL-6&COX-2) in the heart failure zebrafish model. Our study confirmed that the developed SPIONs-loaded NO-RPs are effective tool to alleviate cardiac failure and inflammation in the HF zebrafish model. • Heart failure (HF) is considered one of the main causes of death and morbidity worldwide. Endothelial dysfunction (ED) plays an important role in cardiac disease etiology, where reduced levels of nitric oxide (NO) in the bloodstream leads to vasoconstriction and ED. • The properties of superparamagnetic iron oxide nanoparticles (SPIONs) enable both passive and active delivery of drugs. • Zebrafish is a powerful model for studying heart disease in vertebrates. • SPIONs loaded with nitric oxide releasing nanoparticles (NO-RPs) improved the survival rate in the heart failure zebrafish model and reversed heart failure by enhancing blood flow perfusion in Zebrafish embryos. • SPIONs loaded with NO-RPs significantly reduced the expression of pro-inflammatory markers (lL-6&COX-2) in the heart failure zebrafish model. [ABSTRACT FROM AUTHOR]

Background: The transplantation of endothelial progenitor cells (EPCs) has been shown to reduce neointimal hyperplasia following arterial injury. However, the efficacy of this approach is hampered by limited homing of EPCs to the injury site. Additionally, the in vivo recruitment and metabolic activity of transplanted EPCs have not been continuously monitored. Methods: EPCs were labeled with indocyanine green (ICG)-conjugated superparamagnetic iron oxide nanoparticles (SPIONs) and subjected to external magnetic field targeting to enhance their delivery to a carotid balloon injury (BI) model in Sprague–Dawley rats. Magnetic particle imaging (MPI)/ fluorescence imaging (FLI) multimodal in vivo imaging, 3D MPI/CT imaging and MPI/FLI ex vivo imaging was performed after injury. Carotid arteries were collected and analyzed for pathology and immunofluorescence staining. The paracrine effects were analyzed by enzyme-linked immunosorbent assay. Results: The application of a magnetic field significantly enhanced the localization and retention of SPIONs@PEG-ICG-EPCs at the site of arterial injury, as evidenced by both in vivo continuous monitoring and ex vivo by observation. This targeted delivery approach effectively inhibited neointimal hyperplasia and increased the presence of CD31-positive cells at the injury site. Moreover, serum levels of SDF-1α, VEGF, IGF-1, and TGF-β1 were significantly elevated, indicating enhanced paracrine activity. Conclusions: Our findings demonstrate that external magnetic field-directed delivery of SPIONs@PEG-ICG-EPCs to areas of arterial injury can significantly enhance their therapeutic efficacy. This enhancement is likely mediated through increased paracrine signaling. These results underscore the potential of magnetically guided SPIONs@PEG-ICG-EPCs delivery as a promising strategy for treating arterial injuries.

Integrating hyperthermia with conventional cancer therapies shows promise in improving treatment efficacy while mitigating their side effects. Nanotechnology-based hyperthermia, particularly using superparamagnetic iron oxide nanoparticles (SPIONs), offers a simplified solution for cancer treatment. In this study, we developed composites of SPION quantum dots (Fe3O4) with reduced graphene oxide (Fe3O4/RGO) using the coprecipitation method and investigated their potential application in magnetic hyperthermia. The size of Fe3O4 nanoparticles was controlled within the quantum dot range (≤10 nm) by varying the synthesis parameters, including reaction time as well as the concentration of ammonia and graphene oxide, where their biocompatibility was further improved with the inclusion of polyethylene glycol (PEG). These nanocomposites exhibited low cytotoxic effects on healthy cells (CHO-K1) over an incubation period of 24 h, though the inclusion of PEG enhanced their biocompatibility for longer incubation periods over 48 h. The Fe3O4/RGO composites dispersed in acidic pH buffer (pH 4.66) exhibited considerable heating effects, with the solution temperature increasing by ~10 °C within 5 min of exposure to pulsed magnetic fields, as compared to their dispersions in phosphate buffer and aqueous dimethylsulfoxide solutions. These results demonstrated the feasibility of using quantum dot Fe3O4/RGO composites for magnetic hyperthermia-based therapy to treat cancer, with further studies required to systematically optimize their magnetic properties and evaluate their efficacy for in vitro and in vivo applications.

A novel class of nanomaterials as subunit nano vaccines has shown great potential for delivering antigens to the target in a safe and effective manner. Herein, functionalized superparamagnetic iron oxide nanoparticle (SPION) surfaces with conjugated a malaria protein (vaccine) and carboxyl groups have a comparatively high capacity to bind protein. SPIONs were synthesized using the chemical coprecipitation process, then coated with either 3-aminopropyltriethoxysilane or with PEG plus APTS and characterized using DSL-zeta potential, VSM, TG and SEM. Furthermore, SDS-PAGE was used to measure the amount of protein specifically attached to particles. The idea behind this project is that by gradually and continuously releasing the antigen, it could trigger and sustain a strong immune response over an extended period. The results showed that functionalized SPIONs conjugated to the PyMSP119 antigen might be exploited for the antigen's controlled release and could be applied to various types of antigens in the future. The current study results demonstrated the effectiveness of SPIONS-based antigen vaccination systems for eliciting antibody responses that may be suitable for a variety of illnesses not just malaria. [ABSTRACT FROM AUTHOR]

Nanostructured scaffolds based on cellulose with advanced performances and personalized morphologies for bone tissue engineering are under technological development. 3D-printing and supercritical carbon dioxide (scCO2) technologies are innovative processing strategies that, when combined, allow the precise fabrication of highly porous aerogel scaffolds. Novel sterile cellulose-in-cellulose aerogels decorated with superparamagnetic iron oxide nanoparticles (SPIONs) are synthesized in this work by an integrated technological platform based on 3D-printing and scCO2. Methylcellulose (MC) and bacterial nanocellulose (BC) are two versatile cellulosic polysaccharides with remarkable physicochemical and biological performances, whereas SPIONs are commonly used to functionalize biomaterials aimed at tissue engineering. Aerogels with hierarchical porosity and high structural resolution were obtained according to nitrogen adsorption–desorption analysis, confocal, scanning and transmission microscopies (SEM and TEM). The magnetic properties of SPIONs-doped aerogels confirmed the correct functionalization of the nanostructures. Finally, NIH/3T3 fibroblast cell viability, hemocompatibility with human blood and safety tests (in ovo with HET-CAM and in vivo with Artemia salina) indicate the biocompatibility of the cellulose-in-cellulose aerogels. [ABSTRACT FROM AUTHOR]

Superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as cutting-edge materials, garnering increasing attention in recent years within the fields of chemical and biomedical engineering. This increasing interest is primarily attributed to the distinctive chemical and physical properties of SPIONs. Progress in nanotechnology and particle synthesis methodologies has facilitated the fabrication of SPIONs with precise control over parameters such as composition, size, shape, stability, and magnetic response. Notably, these functionalized materials exhibit a remarkable surface-area-to-volume ratio, biocompatibility, and, most importantly, they can be effectively manipulated using external magnetic fields. Due to these exceptional properties, SPIONs have found widespread utility in the medical field for targeted drug delivery and cell separation, as well as in the chemical engineering field, particularly in wastewater treatment. Magnetic separation techniques driven by magnetophoresis have proven to be highly efficient, encompassing both high-gradient magnetic separation (HGMS) and low-gradient magnetic separation (LGMS). This review aims to provide an in-depth exploration of magnetic field gradient separation techniques, alongside a comprehensive discussion of the applications of SPIONs in the context of drug delivery, cell separation, and environmental remediation. [ABSTRACT FROM AUTHOR]

The detection of magnetic nanoparticles in a liquid medium and the quantification of their concentration have the potential to improve the efficiency of several relevant applications in different fields, including medicine, environmental remediation, and mechanical engineering. To this end, sensors based on the magneto-impedance effect have attracted much attention due to their high sensitivity to the stray magnetic field generated by magnetic nanoparticles, their simple fabrication process, and their relatively low cost. To improve the sensitivity of these sensors, a multidisciplinary approach is required to study a wide range of soft magnetic materials as sensing elements and to customize the magnetic properties of nanoparticles. The combination of magneto-impedance sensors with ad hoc microfluidic systems favors the design of integrated portable devices with high specificity towards magnetic ferrofluids, allowing the use of very small sample volumes and making measurements faster and more reliable. In this work, a magneto-impedance sensor based on an amorphous Fe73.5Nb3Cu1Si13.5B9 wire as the sensing element is integrated into a customized millifluidic chip. The sensor detects the presence of magnetic nanoparticles in the ferrofluid and distinguishes the different stray fields generated by single-domain superparamagnetic iron oxide nanoparticles or magnetically blocked Co-ferrite nanoparticles.

The main goal of this work was to evaluate the therapeutic potential of green superparamagnetic iron oxide nanoparticles (SPIONs) produced with coconut water for treating cutaneous leishmaniasis caused by Leishmania amazonensis. Optical and electron microscopy techniques were used to evaluate the effects on cell proliferation, infectivity percentage, and ultrastructure. SPIONs were internalized by both parasite stages, randomly distributed in the cytosol and located mainly in membrane-bound compartments. The selectivity index for intracellular amastigotes was more than 240 times higher compared to current drugs used to treat the disease. The synthesized SPIONs showed promising activity against Leishmania and can be considered a strong candidate for a new therapeutic approach for treating leishmaniases.

Bernhard Friedrich,1 Rainer Tietze,1 Michaela Dümig,2 Alexandru Sover,3 Marius-Andrei Boca,3 Eveline Schreiber,1 Julia Band,1 Christina Janko,1 Sven Krappmann,2 Christoph Alexiou,1,* Stefan Lyer1,4,* 1Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, Universitätsklinikum Erlangen, Erlangen, Germany; 2Mikrobiologisches Institut – Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany; 3Faculty of Engineering, Ansbach University of Applied Sciences, Ansbach, Germany; 4Department of Otorhinolaryngology, Head and Neck Surgery, Section of Experimental Oncology and Nanomedicine (SEON), Professorship for AI-Controlled Nanomaterials, Universitätsklinikum Erlangen, Erlangen, Germany*These authors contributed equally to this workCorrespondence: Stefan Lyer, Section of Experimental Oncology & Nanomedicine (SEON), Glückstraße 10a, Erlangen, 91054, Germany, Tel +49-9131-85-33142, Fax +49-9131-85-34828, Email stefan.lyer@uk-erlangen.dePurpose: Magnetic separation of microbes can be an effective tool for pathogen identification and diagnostic applications to reduce the time needed for sample preparation. After peptide functionalization of superparamagnetic iron oxide nanoparticles (SPIONs) with an appropriate interface, they can be used for the separation of sepsis-associated yeasts like Candida albicans. Due to their magnetic properties, the magnetic extraction of the particles in the presence of an external magnetic field ensures the accumulation of the targeted yeast.Materials and Methods: In this study, we used SPIONs coated with 3-aminopropyltriethoxysilane (APTES) and functionalized with a peptide originating from GP340 (SPION-APTES-Pep). For the first time, we investigate whether this system is suitable for the separation and enrichment of Candida albicans, we investigated its physicochemical properties and by thermogravimetric analysis we determined the amount of peptide on the SPIONs. Further, the toxicological profile was evaluated by recording cell cycle and DNA degradation. The separation efficiency was investigated using Candida albicans in different experimental settings, and regrowth experiments were carried out to show the use of SPION-APTES-Pep as a sample preparation method for the identification of fungal infections.Conclusion: SPION-APTES-Pep can magnetically remove more than 80% of the microorganism and with a high selective host-pathogen distinction Candida albicans from water-based media and about 55% in blood after 8 minutes processing without compromising effects on the cell cycle of human blood cells. Moreover, the separated fungal cells could be regrown without any restrictions.Keywords: Candida albicans, SPIONs, fungal sepsis, GP340, microbiological identification

In this study, a novel human-size handheld magnetic particle imaging (MPI) system was developed for the high-precision detection of sentinel lymph nodes for breast cancer. The system consisted of a highly sensitive home-made MPI detection probe, a set of concentric coils pair for spatialization, a solenoid coil for uniform excitation at 8 kHz@1.5 mT, and a full mirrored coil set positioned far away from the scanning area. The mirrored coils formed an extremely effective differential pickup structure which suppressed the system noise as high as 100 dB. The different combination of the inner and outer gradient current made the field free point (FFP) move in the Z direction with a uniform intensity of 0.54T/m, while the scanning in the XY direction was implemented mechanically. The third-harmonic signal of the Superparamagnetic Iron Oxide Nanoparticles (SPIONs) at the FFP was detected and then reconstructed synchronously with the current changes. Experiment results showed that the tomographic detection limit was 30 mm in the Z direction, and the sensitivity was about 10 μg Fe SPIONs at 40 mm distance with a spatial resolution of about 5 mm. In the rat experiment, 54 μg intramuscular injected SPIONs were detected successfully in the sentinel lymph node, in which the tracer content was about 1.2% total injected Fe. Additionally, the effective detection time window was confirmed from 4 to 6 min after injection. Relevant clinical ethics are already in the application process. Large mammalian SLNB MPI experiments and 3D preoperative SLNB imaging will be performed in the future.

Addressing the challenge of promoting directional axonal regeneration in a hostile astrocytic scar, which often impedes recovery following spinal cord injury (SCI), remains a daunting task. Cell transplantation is a promising strategy to facilitate nerve restoration in SCI. In this research, a pro‐regeneration system is developed, namely miR‐26a@SPIONs‐OECs, for olfactory ensheathing cells (OECs), a preferred choice for promoting nerve regeneration in SCI patients. These entities show high responsiveness to external magnetic fields (MF), leading to synergistic multimodal cues to enhance nerve regeneration. First, an MF stimulates miR‐26a@SPIONs‐OECs to release extracellular vesicles (EVs) rich in miR‐26a. This encourages axon growth by inhibiting PTEN and GSK‐3β signaling pathways in neurons. Second, miR‐26a@SPIONs‐OECs exhibit a tendency to migrate and orientate along the direction of the MF, thereby potentially facilitating neuronal reconnection through directional neurite elongation. Third, miR‐26a‐enriched EVs from miR‐26a@SPIONs‐OECs can interact with host astrocytes, thereby diminishing inhibitory cues for neurite growth. In a rat model of SCI, the miR‐26a@SPIONs‐OECs system led to significantly improved morphological and motor function recovery. In summary, the miR‐26a@SPIONS‐OECs pro‐regeneration system offers innovative insights into engineering exogenous cells with multiple additional cues, augmenting their efficacy for stimulating and guiding nerve regeneration within a hostile astrocytic scar in SCI. [ABSTRACT FROM AUTHOR]

Purpose: Magnetic particle imaging (MPI) is being explored in biological contexts that require accurate and reproducible quantification of superparamagnetic iron oxide nanoparticles (SPIONs). While many groups have focused on improving imager and SPION design to improve resolution and sensitivity, a few have focused on improving quantification and reproducibility of MPI. The aim of this study was to compare MPI quantification results by two different systems and the accuracy of SPION quantification performed by multiple users at two institutions. Procedures: Six users (3 from each institute) imaged a known amount of Vivotrax + (10 μg Fe), diluted in a small (10 μL) or large (500 μL) volume. These samples were imaged with or without calibration standards in the field of view, to create a total of 72 images (6 users × triplicate samples × 2 sample volumes × 2 calibration methods). These images were analyzed by the respective user with two region of interest (ROI) selection methods. Image intensities, Vivotrax + quantification, and ROI selection were compared across users, within and across institutions. Results: MPI imagers at two different institutes produce significantly different signal intensities, that differ by over 3 times for the same concentration of Vivotrax +. Overall quantification yielded measurements that were within ± 20% from ground truth; however, SPION quantification values obtained at each laboratory were significantly different. Results suggest that the use of different imagers had a stronger influence on SPION quantification compared to differences arising from user error. Lastly, calibration conducted from samples in the imaging field of view gave the same quantification results as separately imaged samples. Conclusions: This study highlights that there are many factors that contribute to the accuracy and reproducibility of MPI quantification, including variation between MPI imagers and users, despite pre-defined experimental setup, image acquisition parameters, and ROI selection analysis. [ABSTRACT FROM AUTHOR]

Many available chemotherapeutic methods are faced with multiple challenges that range from therapeutic failure to detrimental adverse or toxicity effects. Most of the drugs have low efficacy due to low capability to target specific diseased tissues, minimal biocompatibility and low bioavailability. As a result, they are burden to patients by inducing drug resistance, economic losses and even death. The discovery and utilization of nano-based drug carriers such as superparamagnetic iron oxide nanoparticles (SPIONs) in drug delivery system (DDS) has been a great achievement for overcoming the pre-existing challenges. After properly coated and appropriately functionalized, they exhibit extensive drug-loading capacity and are able to be circulated in the blood stream without causing immune provocation before achieving the desired therapeutic effects by delivering drug specifically to the targeted site. Furthermore, they can be remotely controlled to release drugs using appropriate stimuli. Therefore, this review has explained important aspects about the utilization of SPIONs as a novel nano-vector for DDS, focusing on their post-synthetic surface modification, functionalization, drug loading and release. This work is potential as it provides a framework into the applications of SPIONs in theranostics of challenging diseases such as cancer by laying down the basic principles of SPION applications in biomedical field. [ABSTRACT FROM AUTHOR]

Abstract Addressing the challenge of promoting directional axonal regeneration in a hostile astrocytic scar, which often impedes recovery following spinal cord injury (SCI), remains a daunting task. Cell transplantation is a promising strategy to facilitate nerve restoration in SCI. In this research, a pro‐regeneration system is developed, namely miR‐26a@SPIONs‐OECs, for olfactory ensheathing cells (OECs), a preferred choice for promoting nerve regeneration in SCI patients. These entities show high responsiveness to external magnetic fields (MF), leading to synergistic multimodal cues to enhance nerve regeneration. First, an MF stimulates miR‐26a@SPIONs‐OECs to release extracellular vesicles (EVs) rich in miR‐26a. This encourages axon growth by inhibiting PTEN and GSK‐3β signaling pathways in neurons. Second, miR‐26a@SPIONs‐OECs exhibit a tendency to migrate and orientate along the direction of the MF, thereby potentially facilitating neuronal reconnection through directional neurite elongation. Third, miR‐26a‐enriched EVs from miR‐26a@SPIONs‐OECs can interact with host astrocytes, thereby diminishing inhibitory cues for neurite growth. In a rat model of SCI, the miR‐26a@SPIONs‐OECs system led to significantly improved morphological and motor function recovery. In summary, the miR‐26a@SPIONS‐OECs pro‐regeneration system offers innovative insights into engineering exogenous cells with multiple additional cues, augmenting their efficacy for stimulating and guiding nerve regeneration within a hostile astrocytic scar in SCI.

The cross-talk between the EGFR (Epidermal Growth Factor Receptor) and MET (Hepatocyte Growth Factor Receptor) poses a significant challenge in the field of molecular signaling. Their intricate interplay leads to dysregulation and contributes to cancer progression and therapeutic resistance. β-Sitosterol (BS), a plant sterol with promising anticancer properties, shows increased research on its potential as a chemopreventive agent. However, significant modifications are required to deliver BS in cancer cells due to its lower efficacy. The present work aims to design a carrier-mediated delivery system specifically targeting cancer cells with EGFR and MET receptor cross-talk. Surface modification of BS was performed with superparamagnetic iron oxide nanoparticles (SPIONs), polyethylene glycol (PEG), and poly(N-isopropylacrylamide) (PNIPAM) to enhance the delivery of BS at the target site. BS was conjugated with SPIONs (BS-S), PNIPAM (BS-SP), PEG, and PNIPAM (BS-SPP) polymers, respectively, and the conjugated complexes were characterized. Results showed an increase in size, stability, and monodispersity in the following order, BS-S, BS-SP, and BS-SPP. The drug encapsulation efficiency was observed to be highest in BS-SPP (82.5%), compared to BS-S (61%) and BS-SP (74.9%). Sustained drug release was achieved in both BS-SP (82.6%) and BS-SPP (83%). The IC 50 value of BS, BS-S, BS-SP, and BS-SPP towards MCF 7 was 242 µg/mL,197 µg/mL, 168 µg/mL, and 149 µg/mL, HEPG2 was 274 µg/mL, 261 µg/mL, 233 µg/mL and 207 µg/mL and NCIH 460 was 191 µg/mL, 185 µg/mL, 175 and 164 µg/mL, indicating highest inhibition towards NCIH 460 cells. Our results conclude that β-sitosterol conjugated with SPION, PEG, and PNIPAM could be a potential targeted therapy in inhibiting EGFR and MET receptor-expressing cancer cells. [ABSTRACT FROM AUTHOR]

Iron oxide nanoparticles have been investigated due to their suitable characteristics for diverse applications in the fields of biomedicine, electronics, water or wastewater treatment and sensors. Maghemite, magnetite and hematite are the most widely studied iron oxide particles and have ferrimagnetic characteristics. When very small, however, these particles have superparamagnetic properties and are called superparamagnetic iron oxide nanoparticles (SPIONs). Several methods are used for the production of these particles, such as coprecipitation, thermal decomposition and microemulsion. However, the variables of the different types of synthesis must be assessed to achieve greater control over the particles produced. In some studies, it is possible to compare the influence of variations in the factors for production with each of these methods. Thus, researchers use different adaptations of synthesis based on each objective and type of application. With coprecipitation, it is possible to obtain smaller, more uniform particles with adjustments in temperature, pH and the types of reagents used in the process. With thermal decomposition, greater control is needed over the time, temperature and proportion of surfactants and organic and aqueous phases in order to produce smaller particles and a narrower size distribution. With the microemulsion process, the control of the confinement of the micelles formed during synthesis through the proportions of surfactant and oil makes the final particles smaller and less dispersed. These nanoparticles can be used as additives for the creation of new materials, such as magnetic bacterial cellulose, which has different innovative applications. Composites that have SPIONs, which are produced with greater rigour with regards to their size and distribution, have superparamagnetic properties and can be used in medical applications, whereas materials containing larger particles have ferromagnetic applications. To arrive at a particular particle with specific characteristics, researchers must be attentive to both the mechanism selected and the production variables to ensure greater quality and control of the materials produced. [ABSTRACT FROM AUTHOR]

In this study, we investigated the cytotoxicity of doxorubicin (DOX)-loaded magnetic nanofluids on 4T1 mouse tumor epithelial cells and MDA-MB-468 human triple-negative breast cancer (TNBC) cells. Superparamagnetic iron oxide nanoparticles were synthesized using sonochemical coprecipitation by applying electrohydraulic discharge treatment (EHD) in an automated chemical reactor, modified with citric acid and loaded with DOX. The resulting magnetic nanofluids exhibited strong magnetic properties and maintained sedimentation stability in physiological pH conditions. The obtained samples were characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy, UV-spectrophotometry, dynamic light scattering (DLS), electrophoretic light scattering (ELS), vibrating sample magnetometry (VSM), and transmission electron microscopy (TEM). In vitro studies using the MTT method revealed a synergistic effect of the DOX-loaded citric-acid-modified magnetic nanoparticles on the inhibition of cancer cell growth and proliferation compared to treatment with pure DOX. The combination of the drug and magnetic nanosystem showed promising potential for targeted drug delivery, with the possibility of optimizing the dosage to reduce side-effects and enhance the cytotoxic effect on cancer cells. The nanoparticles' cytotoxic effects were attributed to the generation of reactive oxygen species and the enhancement of DOX-induced apoptosis. The findings suggest a novel approach for enhancing the therapeutic efficacy of anticancer drugs and reducing their associated side-effects. Overall, the results demonstrate the potential of DOX-loaded citric-acid-modified magnetic nanoparticles as a promising strategy in tumor therapy, and provide insights into their synergistic effects. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ObjectiveSuperparamagnetic Iron Oxide Nanoparticles (SPIONs) are widely researched as contrast agents in clinical magnetic resonance imaging (MRI). SPIONs are frequently coated with anti-biofouling substances such as poly(ethylene glycol) (PEG) to prevent protein deposition and improve circulation time in vivo. However, few previous studies have comprehensively examined optimization of SPION MR properties with respect to physicochemical properties of the core SPION and the polymeric coating. The aim of this study is to determine effects of different methods of chemical attachment of a polymer, polymer chain length, and polymer coating density on the MR relaxivities of SPIONs, thereby contributing to a better understanding of the interaction of these parameters and the efficacy of the designed agent.ResultsThese studies indicate that the chemical composition and, in particular, the hydrophobicity/hydrophilicity of the chemical group linking PEG chains to a SPION core may play a larger role in the resulting MR relaxivities than other variable properties such as SPION core size and PEG chain length.ConclusionsThe method of SPION fabrication and chemical composition of the coating play a significant role in the MR relaxivities of the resulting particles. These results should be considered in the fabrication of particles for clinical purposes, particularly when optimization of the MR relaxivities is desired.

Objective(s): Superparamagnetic iron oxide nanoparticles (SPIONs) have been considered promising non-invasive imaging tools in medicine. However, their high surface energy leads to NPs aggregation, while non-targeted SPIONs can cause cytotoxic effects on normal cells. In this work, we evaluated the in vitro potential of polyethyleneimine (PEI)-SPIONs targeted by PNC27 peptide as a double targeting agent throughout early cancer diagnosis.Materials and Methods: Initially, PEI was conjugated to PNC27 with HDM-2-binding domain. Then, SPIONs were loaded into PEI-PNC27 through the ligand exchange method. The physicochemical characteristics of the synthesized NPs were evaluated. The cytotoxicity and targeting efficiency were assayed against HT-29 and CT-26 cell lines along with NIH-3t3 as normal cells by MTT method and Prussian blue staining test, respectively. Results: The mean diameter of synthesized carriers was obtained in the range of 86.6 – 116.1 nm with a positive charge. According to the cytotoxicity results, the binding and uptake abilities of the PNC27 peptide by cancer cells were significantly higher than that of the NIH-3t3 cells. However, the results were indicative of the more toxic impacts of targeted synthesized NPs against CT-26 cancer cell line when being compared with HT-29 cells, which may be caused by the different cytotoxicity mechanisms of NPs. In addition, the targeted carriers and SPIONs were present inside and around the cells with HDM-2 expression along with only a few non-targeted vectors, while displaying no appearance throughout the normal cell.Conclusion: The results indicated the efficiency of targeted PEI-coated SPIONs for cancer diagnostic applications.

Recent research has shown that etoposide (ETP), an immunomodulatory medication, can have cytotoxic effects. When accompanied by nano-drug delivery, this possibility can lead to a more effective treatment for cancer. This study involved the delivery of ETP via PDA@SPIONs (termed as ETP-PDA@SPIONs), which are superparamagnetic iron oxide nanoparticles (SPIONs) that have been coated with polydopamine (PDA) and utilized to treat C6 and U87 glioma cancer cell lines. The particle diameter, polydispersive index (PDI), zeta potential, and shape of nanoparticles were determined. The fabricated nanoparticles had a mean particle size of 164 ± 7 nm and a − 37 ± 3 mv zeta potential. Cell lines were tested for sensitivity to PDA@SPIONs, free-ETP, and ETP-PDA@SPIONs. On the cell lines, we tested the proliferation of PDA@SPIONs, free-ETP, and PDA@SPIONs loaded with ETP. The cytotoxicity of ETP-PDA@SPIONs was substantially higher than that of free-ETP-treated cells. The cells' morphological changes were examined by dual staining (acridine orange/ethidium bromide, AO/EB) and nuclear staining methods. Interestingly, this inhibitory impact was not ascribed to the known cellular membrane destruction, cell membrane damage, and reactive oxygen species (ROS). Further tests demonstrated that the nanoparticles substantially impacted mitochondrial functioning, resulting in an aberrant mitochondrial shape, and reduced mitochondrial membrane potential (MMP). Future studies into glioma cancer therapy may want to investigate using the proposed ETP-loaded nanoparticles. [Display omitted] • We establish that Etoposide with polydopamine coated superparamagnetic iron oxide nanoparticles. • The particle diameter, polydispersive index, zeta potential, and shape of nanoparticles were determined. • C6 and U87 glioma cells were tested cytotoxicity by MTT assay. • The cells' morphological changes were examined by acridine orange/ethidium bromide and nuclear staining. • Nanoparticles were induced apoptosis in mitocandrial membrane potential and reactive oxygen species pathway. [ABSTRACT FROM AUTHOR]

Superparamagnetic iron oxide nanoparticles (SPIONs) coated with the synthetic hydrophilic biocompatible polymer polyvinyl alcohol were synthesized using the aqueous method. Static and dynamic magnetization processes were investigated for surface-modified SPIONs by analyzing the magnetization study at constant and varying magnetic fields. The magnetization on the applied magnetic field (M–H) and the magnetization dependent on temperature (M–T) were investigated. The temperature dependence of the complex susceptibility of SPIONs was investigated by measuring the in-phase (natural) and out-of-phase (imaginary) components of the susceptibility value at a frequency of 10 Hz and a very low magnetizing field. The XRD study shows diffraction peaks consistent with the magnetite (Fe3O4) phase of SPIONPs. FTIR, DSC, and TGA studies confirm the functional groups and stability of the coated nanoparticles. The magnetizing field cycle study at various constant temperatures (10, 100, and 300 K) shows the high magnetization value of polyvinyl alcohol-coated SPIONs with superparamagnetic states at and above 300 K. The effect of interparticle interaction on blocking temperature has been interpreted from FC/ZFC curves drawn at different DC magnetizing field values by varying temperature between 10 and 300 K. [ABSTRACT FROM AUTHOR]

In this work, Curcuma longa L. extract has been used in the synthesis and direct coating of magnetite (Fe3O4) nanoparticles ~12 nm, providing a surface layer of polyphenol groups (–OH and –COOH). This contributes to the development of nanocarriers and triggers different bio-applications. Curcuma longa L. is part of the ginger family (Zingiberaceae); the extracts of this plant contain a polyphenol structure compound, and it has an affinity to be linked to Fe ions. The nanoparticles' magnetization obtained corresponded to close hysteresis loop Ms = 8.81 emu/g, coercive field Hc = 26.67 Oe, and low remanence energy as iron oxide superparamagnetic nanoparticles (SPIONs). Furthermore, the synthesized nanoparticles (G-M@T) showed tunable single magnetic domain interactions with uniaxial anisotropy as addressable cores at 90–180°. Surface analysis revealed characteristic peaks of Fe 2p, O 1s, and C 1s. From the last one, it was possible to obtain the C–O, C=O, –OH bonds, achieving an acceptable connection with the HepG2 cell line. The G-M@T nanoparticles do not induce cell toxicity in human peripheral blood mononuclear cells or HepG2 cells in vitro, but they can increase the mitochondrial and lysosomal activity in HepG2 cells, probably related to an apoptotic cell death induction or to a stress response due to the high concentration of iron within the cell. [ABSTRACT FROM AUTHOR]

Circulating tumor clusters (CTC) disseminating from the primary tumor are responsible for secondary tumor formation where the conventional treatments such as chemotherapy and radiotherapy does not prevent the metastasis at locally advanced stage of breast cancer. In this study, a smart nanotheranostic system has been developed to track and eliminate the CTCs before it can colonize at a new site, which would reduce metastatic progression and increase the five-year survival rate of the breast cancer patients. Targeted multiresponsive (magnetic hyperthermia and pH) nanomicelles incorporated with NIR fluorescent superparamagnetic iron oxide nanoparticles were developed based on self-assembly for dual modal imaging and dual toxicity for spontaneous killing of CTCs in blood stream. A heterogenous tumor clusters model was developed to mimic the CTCs isolated from breast cancer patients. The nanotheranostic system was further evaluated for the targeting property, drug release kinetics, hyperthermia and cytotoxicity against developed CTC model in vitro. In vivo model in BALB/c mice equivalent to stage III and IV human metastatic breast cancer was developed to evaluate the biodistribution and therapeutic efficacy of micellar nanotheranostic system. Reduced CTCs in blood stream and low distant organ metastasis after treatment with the nanotheranostic system demonstrates its potential to capture and kill the CTCs that minimize the secondary tumor formation at distant sites. Targeted elimination of CD44 expressing circulating tumor clusters (CTC) using smart nanotheranostics prevented secondary colonization and tumor progression in immunocompetent CTC model in mice. [Display omitted] [ABSTRACT FROM AUTHOR]

This study was performed to synthesize a radiopharmaceutical designed for multimodal hepatocellular carcinoma (HCC) treatment involving radionuclide therapy and magnetic hyperthermia. To achieve this goal, the superparamagnetic iron oxide (magnetite) nanoparticles (SPIONs) were covered with a layer of radioactive gold (198Au) creating core–shell nanoparticles (SPION@Au). The synthesized SPION@Au nanoparticles exhibited superparamagnetic properties with a saturation magnetization of 50 emu/g, which is lower than reported for uncoated SPIONs (83 emu/g). Nevertheless, the SPION@Au core–shell nanoparticles showed a sufficiently high saturation magnetization value which allows them to reach a temperature of 43 °C at a magnetic field frequency of 386 kHz. The cytotoxic effect of nonradioactive and radioactive SPION@Au–polyethylene glycol (PEG) bioconjugates was carried out by treating HepG2 cells with various concentrations (1.25–100.00 µg/mL) of the compound and radioactivity in range of 1.25–20 MBq/mL. The moderate cytotoxic effect of nonradioactive SPION@Au-PEG bioconjugates on HepG2 was observed. The cytotoxic effect associated with the β− radiation emitted by 198Au was much greater and already reaches a cell survival fraction below 8% for 2.5 MBq/mL of radioactivity after 72 h. Thus, the killing of HepG2 cells in HCC therapy should be possible due to the combination of the heat-generating properties of the SPION-198Au–PEG conjugates and the radiotoxicity of the radiation emitted by 198Au. [ABSTRACT FROM AUTHOR]

Core–shell superparamagnetic iron oxide nanoparticles hold great promise as a theranostic platform in biological systems. Herein, we report the biological effect of multifunctional cyclodextrin-appended SPIONs (CySPION) in mutant Npc1-deficient CHO cells compared to their wild type counterparts. CySPIONs show negligible cytotoxicity while they are strongly endocytosed and localized in the lysosomal compartment. Through their bespoke pH-sensitive chemistry, these nanoparticles release appended monomeric cyclodextrins to mobilize over-accumulated cholesterol and eject it outside the cells. CySPIONs show a high rate of transport across blood–brain barrier models, indicating their promise as a therapeutic approach for cholesterol-impaired diseases affecting the brain. [ABSTRACT FROM AUTHOR]

In the emerging field of nanomedicine, nanoparticles have been widely considered as drug carriers and are now used in various clinically approved products. Therefore, in this study, we synthesized superparamagnetic iron-oxide nanoparticles (SPIONs) via green chemistry, and the SPIONs were further coated with tamoxifen-conjugated bovine serum albumin (BSA-SPIONs-TMX). The BSA-SPIONs-TMX were within the nanometric hydrodynamic size (117 ± 4 nm), with a small poly dispersity index (0.28 ± 0.02) and zeta potential of −30.2 ± 0.09 mV. FTIR, DSC, X-RD, and elemental analysis confirmed that BSA-SPIONs-TMX were successfully prepared. The saturation magnetization (Ms) of BSA-SPIONs-TMX was found to be ~8.31 emu/g, indicating that BSA-SPIONs-TMX possess superparamagnetic properties for theragnostic applications. In addition, BSA-SPIONs-TMX were efficiently internalized into breast cancer cell lines (MCF-7 and T47D) and were effective in reducing cell proliferation of breast cancer cells, with IC50 values of 4.97 ± 0.42 μM and 6.29 ± 0.21 μM in MCF-7 and T47D cells, respectively. Furthermore, an acute toxicity study on rats confirmed that these BSA-SPIONs-TMX are safe for use in drug delivery systems. In conclusion, green synthesized superparamagnetic iron-oxide nanoparticles have the potential to be used as drug delivery carriers and may also have diagnostic applications. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a class of highly stable and closed-loop noncoding RNA that are involved in the occurrence and development of hepatocellular carcinoma (HCC). However, little is known about the therapeutic role of circRNAs in HCC. We found that high circ_0058051 expression was negatively correlated with the prognosis of HCC patients. Circ_0058051 knockdown attenuated the proliferation and colony formation, meanwhile inhibited migration of HCC cells. Circ_0058051 may be used as a target for HCC gene therapy. We synthesized a novel small interfering RNA (siRNA) delivery system, PEG-PCL-PEI-C14-SPIONs (PPPCSs), based on superparamagnetic iron oxide nanoparticles (SPIONs). PPPCSs protected the siRNA of circ_0058051 from degradation in serum and effectively delivered siRNA into SMMC-7721 cells. Meanwhile, intravenous injection of the PPPCSs/siRNA complex could inhibit tumor growth in the subcutaneous tumor model. In addition, the nanocomposite is not toxic to the organs of nude mice. The above results show that PPPCSs/si-circ_0058051 complex may provide a novel and promising method of HCC treatment. [ABSTRACT FROM AUTHOR]

Background: Several blood replacements have been developed because of issues with blood collection and storage, increased expenditures, and a global lack of reserves. Studies on artificial blood primarily concentrate on the research and synthesis of molecules that transport oxygen. The primary objective of the current work was to create a supporting, oxygen-carrying biological material that can replace blood and be used to save lives when blood is not available. Methods: The work started with the synthesis of superparamagnetic iron oxide nanoparticles (SPIONS), and two distinct procedures were applied to ensure binding to hemoglobin (Hb) molecules. The surface modifications of the particles were carried out gradually by 3-amino propyl trimethoxy silane (3APGASPIONS) and tartaric acid (TASPIONS). Analysis methods used to characterize the particles include Fourier transform infrared spectrophotometer (FT-IR), elemental analysis (EDX), scanning electron microscope (SEM), X-ray diffractometry (XRD), and high contrast transmission electron microscopy (C-TEM). The characterization studies of SPIONS which bind Hb molecules to the surface were repeated and their effects on endothelial cell culture were examined to determine their toxic effects in vitro. Cell proliferation, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity changes were assessed in the evaluation of the possible toxic effects of the cells against the treated particles in the prepared cell lines. Blood substitute solutions synthesized by two different methods were stored on the shelf for about 1 month and the results were compared with fresh Hb solutions. Results and Conclusion: The CV and UV analysis results obtained from artificial Hb substitutes revealed that the structural integrity of Hb molecules did not change, the oxygen transport capabilities of biomolecules were preserved, and this state remained stable for a long time. Furthermore, it was determined that nanocomplexes synthesized by the two methods caused different cellular proliferation and there was a more limited increase in cellular enzyme activities (SOD, CAT, GPx) of Hb-bound particle solutions when compared to pure SPIONS.

Aim: To explore the antidiabetic effect of superparamagnetic iron oxide nanoparticles (SPIONs)-PEG-550 and its related metabolic pathways in muscles and kidney. Materials & methods: Diabetes was induced in 5-day neonatal rats; after confirming diabetes, treatment with SPIONs-PEG-550 started at different doses for 4 weeks. Routine analysis of glucose, insulin, adipocytokines, urea and creatinine was performed. The expression of several genes involved in metabolic pathways and the corresponding protein levels were examined. Results & conclusion: SPIONs-PEG-550 normalized the disturbed glucose homeostasis, reversed insulin resistance, adjusted the serum level of adipocytokines, and improved several disturbed downstream effectors of the insulin signaling and WNT pathway in both tissues. Histological examination of the muscle and pancreas has shown almost normal functional characteristics without remarkable adverse effects on the kidney. [ABSTRACT FROM AUTHOR]

Superparamagnetic iron oxide nanoparticles (SPIONs) may act as an excellent theragnostic tool if properly coated and stabilized in a biological environment, even more, if they have targeting properties towards a specific cellular target. Humanized Archaeoglobus fulgidus Ferritin (HumAfFt) is an engineered ferritin characterized by the peculiar salt-triggered assembly-disassembly of the hyperthermophile Archaeoglobus fulgidus ferritin and is successfully endowed with the human H homopolymer recognition sequence by the transferrin receptor (TfR1 or CD71), overexpressed in many cancer cells in response to the increased demand of iron. For this reason, HumAfFt was successfully used in this study as a coating material for 10 nm SPIONs, in order to produce a new magnetic nanocarrier able to discriminate cancer cells from normal cells and maintain the potential theragnostic properties of SPIONs. HumAfFt-SPIONs were exhaustively characterized in terms of size, morphology, composition, and cytotoxicity. The preferential uptake capacity of cancer cells toward HumAfFt-SPIONs was demonstrated in vitro on human breast adenocarcinoma (MCF7) versus normal human dermal fibroblast (NHDF) cell lines. [ABSTRACT FROM AUTHOR]

Ammonia is a serious contaminant of aquaculture water due to its continuous release into the water environment during the biological processes of aquatic animals. Ammonia accumulation in water has negative environmental impacts, including eutrophication and the death of aquatic organisms. Therefore, sensitive and accurate determination of ammonia is an urgent need, especially in pisciculture systems. Here, we report the fabrication of a novel magnetic–hyperbranched nanomaterial-based ammonia-sensing probe for the fast and sensitive determination of ammonia in water. The proposed probe is composed of poly(amidoamine) (PAMAM)-coated superparamagnetic iron oxide nanoparticles (SPIONs) decorated with silver nanoparticles. Changing the ammonia concentration is associated with a corresponding change in the surface plasmon resonance property of silver nanoparticles. The proposed nanosystem was characterized with FTIR spectroscopy, SEM imaging, energy-dispersive X-ray (EDX) analysis, TEM imaging, X-ray diffractometry (XRD), and vibrating sample magnetometry (VSM). The TEM images showed a homogenous and uniform distribution of the nanoparticles with an average nanoparticle size of 200 nm, while the surface silver nanoparticles have an average particle size of 10–50 nm. The proposed optical ammonia sensor was successfully used to determine the concentration of ammonia in water samples by measuring the change in the solution absorbance at 428 nm. The obtained results revealed high recovery values (96.3–104.7%) and very low detection (LOD = 5.69 mg/L) and quantification (LOQ = 18.96 mg/L) limits. The standard plot is linear in the concentration range of 10–50 mg/L with an r2 value of 0.9980. Sandell's sensitivity of the most promising sensor (NP-III) among the investigated systems was found to be 0.15 µg/cm2, which indicates high sensitivity. [ABSTRACT FROM AUTHOR]

Chemical co-precipitation from ferrous and ferric salts at a 1:1.9 stoichiometric ratio in NH4OH base with ultrasonication (sonolysis) in a low vacuum environment has been used for obtaining colloidal suspensions of Fe3O4 nanoparticles coated with citric acid. Before coating, the nanoparticles were processed by electrohydraulic discharges with a high discharge current (several tens of amperes) in a water medium using a pulsed direct current. Magnetite nanoparticles were obtained with an average crystallite diameter D = 25–28 nm as obtained by XRD and particle sizes of 25 nm as measured by small-angle X-ray scattering. Magnetometry showed that all samples were superparamagnetic. The saturation magnetization for the citric acid covered samples after electrohydraulic processing showed higher value (58 emu/g) than for the directly coated samples (50 emu/g). Ultraviolet-visible spectroscopy and Fourier transform infrared spectroscopy showed the presence and binding of citric acid to the magnetite surface by chemisorption of carboxylate ions. Hydrodynamic sizes obtained from DLS and zeta potentials were 93 and 115 nm, −26 and −32 mV for the citric acid covered nanoparticles and 226 nm and 21 mV for the bare nanoparticles, respectively. The hydraulic discharge treatment resulted in a higher citric acid coverage and better particle dispersion. The developed method can be used in nanoparticle synthesis for biomedical applications. [ABSTRACT FROM AUTHOR]

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Size and zeta potential are critical physicochemical properties of nanoparticles (NPs), influencing their biological activity and safety profile. These are essential for further industrial upscale and clinical success. However, the characterization of polydisperse, non-spherical NPs is a challenge for traditional characterization techniques (ex., dynamic light scattering (DLS)). In this paper, superparamagnetic iron oxide nanoparticles (SPIONs) were coated with polyvinyl alcohol (PVAL) exhibiting different terminal groups at their surface, either hydroxyl (OH), carboxyl (COOH) or amino (NH2) end groups. Size, zeta potential and concentration were characterized by orthogonal methods, namely, batch DLS, nanoparticle tracking analysis (NTA), tunable resistive pulse sensing (TRPS), transmission electron microscopy (TEM), asymmetric flow field flow fractionation (AF4) coupled to multi-angle light scattering (MALS), UV–Visible and online DLS. Finally, coated SPIONs were incubated with albumin, and size changes were monitored by AF4-MALS-UV-DLS. NTA showed the biggest mean sizes, even though DLS PVAL-COOH SPION graphs presented aggregates in the micrometer range. TRPS detected more NPs in suspension than NTA. Finally, AF4-MALS-UV-DLS could successfully resolve the different sizes of the coated SPION suspensions. The results highlight the importance of combining techniques with different principles for NPs characterization. The advantages and limitations of each method are discussed here. [ABSTRACT FROM AUTHOR]

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) have shown great potential for being utilized in Nanocarriers (NCs) applications throughout the Drug Delivery System (DDS). However, there are several obstacles to make a practical magnetic NCs, such as low dispersity and high toxicity in the biological systems, and also low surface area for drug loading. In this work, magnetic NCs have been synthesized through a facile three-step process, first SPIONs were synthesized by the co-precipitation method, then decorated via mesoporous silica and finally the calcinated NCs functionalized with NH2 by a simple process in the ethanol solvent. The structure and morphology of the as-synthesized NCs have been characterized by the usage of different analyzing methods such as XRD, FTIR, TEM, FE-SEM, and TGA. Also, the magnetic properties have been investigated by the means of VSM throughout each step of the procedure. Lastly, we have applied the technique of N2 adsorption-desorption to observe the surface area, pore size, and volume. Besides optimal magnetization of final nanoparticles (30 emu/gr), the as-synthesized NCs claimed the high surface area and small diameter, at 371 m2.g-1 and 70 nm, respectively. Moreover, the functionalized NCs have demonstrated well dispersity over a day in the PBS solution. As a result, the as-prepared nanocarrier able to overcome drug delivery obstacles and used as a potential nanocarrier owing to its small diameter, high surface area/ pore volume, optimal magnetization, and well dispersity in the biological condition. [ABSTRACT FROM AUTHOR]

Nanoparticles are potential candidates for wastewater treatment especially for the removal of heavy metals due to their strong affinity. Many biopolymers are used as adsorbents and encapsulation of nanoparticle onto them can increase their efficiency. In this study, SPIONs, alginate, and SPIONs incorporated on alginate beads have been synthesized and characterized both microscopically and spectroscopically. These were then used for the removal of chromium metal and the percentage of removal was evaluated using a batch adsorption study. The percent removal of chromium using SPIONs, alginate and alginate–SPIONs beads were recorded to be 93%, 91% and 94%, respectively. The adsorption of chromium using SPIONs and alginate–SPIONs beads followed the Tempkin isotherm, whereas adsorption of chromium metal by alginate beads was found to be homogeneous in nature and followed the Langmuir isotherm with an R2 value of 0.9784. An in-vivo study using Danio rerio as a model organism was done to examine the toxicity and the removal efficiency of the samples. It was observed that chromium water treated with alginate–SPIONs beads, which were removed after water treatment showed less damage to the fishes when compared to SPIONs and alginate beads treated with chromium water where the SPIONs and alginate beads were not removed after the treatment period. [ABSTRACT FROM AUTHOR]

The current study presents a bimodal therapeutic platform for cancer treatment. Bimodal implies that the presented drug loaded core-shell structure is capable of elevating the tumor tissue temperature (hyperthermia) through the superparamagnetic iron oxide core and simultaneously release a Poly (ADP-ribose) polymerase-1(PARP-1)-modifying agent from the thermoresponsive shell. Magnetic thermoresponsive nanocomposite MTN was synthesized via an in situ free radical polymerization of thermo-responsive (N-isopropylacrylamide) (NIPAAm) monomer in the presence of 11-nm monodisperse SPIONs. The composite was allowed to swell in various concentrations of the PARP inhibitor: 5-aminoisoquinoline (5-AIQ) forming drug-loaded magnetic thermoresponsive nanocomposite (MTN-5.AIQ). Structural characterization of the formed composite is studied via various experimental tools. To assess the coil to globule transition temperature, the lower critical solution temperature (LCST) is determined by differential scanning calorimetry (DSC) method and the cloud point (Tp) is determined by turbidometry. Magnetic thermoresponsive nanocomposite (MTN) is formed with excellent potential for hyperthermia. A high drug loading efficiency (85.72%) is obtained with convenient temperature dependent drug release kinetics. Biocompatibility and cytotoxic efficacy are tested on an in vivo and in vitro colorectal-adenocarcinoma model, respectively. MTN.5-AIQ administration exhibits normal hepatic and renal functions as well as lower toxic effect on normal tissue. In addition, the composite effectively inhibits Caco-2 cells viability upon incubation. Based on the obtained results, the proposed therapeutic platform can be considered as a novel, promising candidate for dual therapy of colorectal adenocarcinoma exhibiting a PARP-1 overexpression. as well as increased the inhabiting efficacy of 5-AIQ.