The toxicity of superparamagnetic iron oxide nanoparticles induced on the testicular cells: In vitro study.

Superparamagnetic iron oxide nanoparticles (SPIONs) have gained significant attention in biomedical research due to their potential applications. However, little is known about their impact and toxicity on testicular cells. To address this issue, we conducted an in vitro study using primary mouse testicular cells, testis fragments, and sperm to investigate the cytotoxic effects of sodium citrate-coated SPIONs (Cit_SPIONs). Herein, we synthesized and physiochemically characterized the Cit_SPIONs and observed that the sodium citrate diminished the size and improved the stability of nanoparticles in solution during the experimental time. The sodium citrate (measured by thermogravimetry) was biocompatible with testicular cells at the used concentration (3%). Despite these favorable physicochemical properties, the in vitro experiments demonstrated the cytotoxicity of Cit_SPIONs, particularly towards testicular somatic cells and sperm cells. Transmission electron microscopy analysis confirmed that Leydig cells preferentially internalized Cit_SPIONs in the organotypic culture system, which resulted in alterations in their cytoplasmic size. Additionally, we found that Cit_SPIONs exposure had detrimental effects on various parameters of sperm cells, including motility, viability, DNA integrity, mitochondrial activity, lipid peroxidation (LPO), and ROS production. Our findings suggest that testicular somatic cells and sperm cells are highly sensitive and vulnerable to Cit_SPIONs and induced oxidative stress. This study emphasizes the potential toxicity of SPIONs, indicating significant threats to the male reproductive system. Our findings highlight the need for detailed development of iron oxide nanoparticles to enhance reproductive nanosafety.

Green SPIONs as a novel highly selective treatment for leishmaniasis: an in vitro study against Leishmania amazonensis intracellular amastigotes.

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.

Synthesis of Iron Oxides and Influence on Final Sizes and Distribution in Bacterial Cellulose Applications.

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.

Processing and Physicochemical Properties of Magnetite Nanoparticles Coated with Curcuma longa L. Extract.

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.

Biomedical Applications of Iron Oxide Nanoparticles: Current Insights Progress and Perspectives.

The enormous development of nanomaterials technology and the immediate response of many areas of science, research, and practice to their possible application has led to the publication of thousands of scientific papers, books, and reports. This vast amount of information requires careful classification and order, especially for specifically targeted practical needs. Therefore, the present review aims to summarize to some extent the role of iron oxide nanoparticles in biomedical research. Summarizing the fundamental properties of the magnetic iron oxide nanoparticles, the review's next focus was to classify research studies related to applying these particles for cancer diagnostics and therapy (similar to photothermal therapy, hyperthermia), in nano theranostics, multimodal therapy. Special attention is paid to research studies dealing with the opportunities of combining different nanomaterials to achieve optimal systems for biomedical application. In this regard, original data about the synthesis and characterization of nanolipidic magnetic hybrid systems are included as an example. The last section of the review is dedicated to the capacities of magnetite-based magnetic nanoparticles for the management of oncological diseases.

Methylene blue-covered superparamagnetic iron oxide nanoparticles combined with red light as a novel platform to fight non-local bacterial infections: A proof of concept study against Escherichia coli.

Currently, antimicrobial photodynamic therapy (APDT) is limited to the local treatment of topical infections, and a platform that can deliver the photosensitizer to internal organs is highly desirable for non-local ones; SPIONs can be promising vehicles for the photosensitizer. This work reports an innovative application of methylene blue (MB)-superparamagnetic iron oxide nanoparticles (SPIONs). We report on the preparation, characterization, and application of MB-SPIONs for antimicrobial photodynamic therapy. When exposed to light, the MB photosensitizer generates reactive oxygen species (ROS), which cause irreversible damage in microbial cells. We prepare SPIONs by the co-precipitation method. We cover the nanoparticles with a double silica layer - tetraethyl orthosilicate and sodium silicate - leading to the hybrid material magnetite-silica-MB. We characterize the as-prepared SPIONs by Fourier transform infrared spectroscopy, powder X-ray diffraction, and magnetic measurements. We confirm the formation of magnetite using powder X-ray diffraction data. We use the Rietveld method to calculate the average crystallite size of magnetite as being 14 nm. Infrared spectra show characteristic bands of iron­oxygen as well as others associated with silicate groups. At room temperature, the nanocomposites present magnetic behavior due to the magnetite core. Besides, magnetite-silica-MB can promote ROS formation. Thus, we evaluate the photodynamic activity of Fe3O4-silica-MB on Escherichia coli. Our results show the bacteria are completely eradicated following photodynamic treatment depending on the MB release time from SPIONs and energy dose. These findings encourage us to explore the use of magnetite-silica-MB to fight internal infections in preclinical assays.

Biotechnological approach to induce human fibroblast apoptosis using superparamagnetic iron oxide nanoparticles.

Cancer-Associated Fibroblasts (CAFs) contribute to tumour progression and have received significant attention as a therapeutic target. These cells produce growth factors, cytokines and chemokines, stimulating cancer cell proliferation and inhibiting their apoptosis. Recent advances in drug delivery have demonstrated a significant promise of iron oxide nanoparticles in clinics as theranostic agents, mainly due to their magnetic properties. Here, we designed superparamagnetic iron oxide nanoparticles (SPIONs) to induce apoptosis of human fibroblasts. SPIONs were synthesized via co-precipitation method and coated with sodium citrate (SPION_Cit). We assessed the intracellular uptake of SPIONs by human fibroblast cells, as well as their cytotoxicity and ability to induce thermal effects under the magnetic field. The efficiency and time of nanoparticle internalization were assessed by Prussian Blue staining, flow cytometry and transmission electron microscopy. SPIONs_Cit were detected in the cytoplasm of human fibroblasts 15 min after in vitro exposure, entering into cells mainly via endocytosis. Analyses through Cell Titer Blue assay, AnnexinV-fluorescein isothiocyanate (FITC) and propidium iodide (PI) cellular staining demonstrated that concentrations below 8 × 10-2 mg/mL of SPIONs_Cit did not alter cell viability of human fibroblast. Furthermore, it was also demonstrated that SPIONs_Cit associated with alternating current magnetic field were able to induce hyperthermia and human fibroblast cell death in vitro, mainly through apoptosis (83.5%), activating caspase 8 (extrinsic apoptotic via) after a short exposure period. Collectively these findings suggest that our nanoplatform is biocompatible and can be used for therapeutic purposes in human biological systems, such as inducing apoptosis of CAFs.

Superparamagnetic iron-oxide nanoparticles mPEG350- and mPEG2000-coated: cell uptake and biocompatibility evaluation.

Superparamagnetic iron oxide nanoparticles (SPIONS) were synthesized by thermal decomposition of an organometallic precursor at high temperature and coated with a bi-layer composed of oleic acid and methoxy-polyethylene glycol-phospholipid. The formulations were named SPION-PEG350 and SPION-PEG2000. Transmission electron microscopy, X-ray diffraction and magnetic measurements show that the SPIONs are near-spherical, well-crystalline, and have high saturation magnetization and susceptibility. FTIR spectroscopy identifies the presence of oleic acid and of the conjugates mPEG for each sample. In vitro biocompatibility of SPIONS was investigated using three cell lines; up to 100µg/ml SPION-PEG350 showed non-toxicity, while SPION-PEG2000 showed no signal of toxicity even up to 200µg/ml. The uptake of SPIONS was detected using magnetization measurement, confocal and atomic force microscopy. SPION-PEG2000 presented the highest internalization capacity, which should be correlated with the mPEG chain size. The in vivo results suggested that SPION-PEG2000 administration in mice triggered liver and kidney injury. FROM THE CLINICAL EDITOR: The potential use of superparamagnetic iron oxide nanoparticles (SPIONS) in the clinical setting have been studied by many researchers. The authors synthesized two types of SPIONS here and investigated the physical properties and biological compatibility. The findings should provide more data on the design of SPIONS for clinical application in the future.

Transient modulation of acetylcholinesterase activity caused by exposure to dextran-coated iron oxide nanoparticles in brain of adult zebrafish.

Superparamagnetic iron oxide nanoparticles (SPIONs) are of great interest in nanomedicine due to their capability to act simultaneously as a contrast agent and as a targeted drug delivery system. At present, one of the biggest concerns about the use of SPIONs remains around its toxicity and, for this reason, it is important to establish the safe upper limit for each use. In the present study, SPION coated with cross-linked aminated dextran (CLIO-NH2) were synthesized and their toxicity to zebrafish brain was investigated. We have evaluated the effect of different CLIO-NH2 doses (20, 50, 100, 140 and 200 mg/kg) as a function of time after exposure (one, 16, 24 and 48 h) on AChE activity and ache expression in zebrafish brain. The animals exposed to 200 mg/kg and tested 24 h after administration of the nanoparticles have shown decreased AChE activity, reduction in the exploratory performance, significantly higher level of ferric iron in the brains and induction of casp8, casp 9 and jun genes. Taken together, these findings suggest acute brain toxicity by the inhibition of acetylcholinesterase and induction of apoptosis.

In vitro and in vivo experiments with iron oxide nanoparticles functionalized with DEXTRAN or polyethylene glycol for medical applications: magnetic targeting.

In this research work, DEXTRAN- and polyethylene glycol (PEG)-coated iron-oxide superparamagnetic nanoparticles were synthetized and their cytotoxicity and biodistribution assessed. Well-crystalline hydrophobic Fe3 O4 SPIONs were formed by a thermal decomposition process with d = 18 nm and σ = 2 nm; finally, the character of SPIONs was changed to hydrophilic by a post-synthesis procedure with the functionalization of the SPIONs with PEG or DEXTRAN. The nanoparticles present high saturation magnetization and superparamagnetic behavior at room temperature, and the hydrodynamic diameters of DEXTRAN- and PEG-coated SPIONs were measured as 170 and 120 nm, respectively. PEG- and DEXTRAN-coated SPIONs have a Specific Power Absorption SPA of 320 and 400 W/g, respectively, in an ac magnetic field with amplitude of 13 kA/m and frequency of 256 kHz. In vitro studies using VERO and MDCK cell lineages were performed to study the cytotoxicity and cell uptake of the SPIONs. For both cell lineages, PEG- and DEXTRAN-coated nanoparticles presented high cell viability for concentrations as high as 200 µg/mL. In vivo studies were conducted using BALB/c mice inoculating the SPIONs intravenously and exposing them to the presence of an external magnet located over the tumour. It was observed that the amount of PEG-coated SPIONs in the tumor increased by up to 160% when using the external permanent magnetic as opposed to those animals that were not exposed to the external magnetic field.