Polymer-coated Superparamagnetic Iron Oxide Nanoparticles Research Articles

A Novel One-Pot Synthesis of PVP-Coated Iron Oxide Nanoparticles as Biocompatible Contrast Agents for Enhanced T2-Weighted MRI

A contrast agent with specific characteristics is essential for high-quality magnetic resonance imaging (MRI). It plays a crucial role in enhancing the visibility of certain tissues and structures, making it imperative for diagnostic procedures. Superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as a promising alternative to traditional contrast agents for MRI due to their non-toxicity and superior magnetic properties. However, a suitable surface coating strategy is needed to produce polymer-coated SPIONs with controllable sizes in order to enhance their stability and biocompatibility. This study presents a novel one-pot synthesis method for the production of highly stable polyvinylpyrrolidone (PVP)-coated SPIONs. By systematically manipulating the physicochemical properties of SPIONs, the effect of different molecular weights of PVP was studied. The results showed that SPIONs coated with PVP with molecular wight 40,000 g/mol (40 K) exhibited a high magnetization (Ms = 48.4 emu/g), an average size distribution (11.61 nm), and excellent stability. The relaxivity of coated and uncoated SPIONs was investigated using MRI images. The results revealed that the (r2/r1) ratio of PVP40K-SPIONs was 72.55, compared to 55.72 for the bare SPIONs, making them a highly promising T2-contrast agent for future development of MRI applications. This study opens new avenues for the development of biocompatible and stable SPIONs for improved medical diagnostic and imaging.

Polycaprolactone-coated superparamagnetic iron oxide nanoparticles for in vitro magnetic hyperthermia therapy of cancer

Magnetic hyperthermia therapy of cancer is a promising alternative for the current chemotherapy and radiation options, due to its targeting capability and lower systemic toxicity. However, agglomeration vulnerability of the nano-heating agents in aqueous solutions, low control over the heat generation and dissipation at the target region, and eschewed clearance by the renal and reticuloendothelial systems remain as the main challenges for clinical translation of this approach. Here we report superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by using a single precursor, stabilized with a controlled micellar conformation, and coated with a thin polycaprolactone biopolymer shell to achieve enhanced cytocompatibility and thermosensitivity under external alternating magnetic field (AMF) of varied intensities. The in vitro investigations indicated a negligible influence of the polymer-coated SPIONs on cell viability of human liver cancer cells (HepG2) at a maximum concentration of 100 μg∙mL−1. However, the cell viability was reduced significantly to 40.1 ± 0.9% within the secure hyperthermia temperature range achieved by the heating effect of polymer-coated SPIONs in presence of AMF, depicting the on/off cytotoxicity phenomenon of polymer-coated SPIONs under AMF exposure. Therefore, the developed nanostructure presents a step-change as potential targeted nano-heating agents for new therapeutic options.

Complement activation in vitro and reactogenicity of low-molecular weight dextran-coated SPIONs in the pig CARPA model: Correlation with physicochemical features and clinical information

The unique magnetic properties of superparamagnetic iron oxide nanoparticles (SPIONs) have led to their increasing use in drug delivery and imaging applications. Some polymer-coated SPIONs, however, share with many other nanoparticles the potential of causing hypersensitivity reactions (HSRs) known as complement (C) activation-related pseudoallergy (CARPA). In order to explore the roles of iron core composition and particle surface coating in SPION-induced CARPA, we measured C activation by 6 different SPIONs in a human serum that is known to react to nanoparticles (NPs) with strong C activation. Remarkably, only the carboxymethyldextran-coated (ferucarbotran, Resosvist®) and dextran-coated (ferumoxtran-10, Sinerem®) SPIONs caused significant C activation, while the citric acid, phosphatidylcholine, starch and chitosan-coated SPIONs had no such effect. Focusing on Resovist and Sinerem, we found Sinerem to be a stronger activator of C than Resovist, although the individual variation in 15 different human sera was substantial. Further analysis of C activation by Sinerem indicated biphasic dose dependence and significant production of C split product Bb but not C4d, attesting to alternative pathway C activation only at low doses. Consistent with the strong C activation by Sinerem and previous reports of HSRs in man, injection of Sinerem in a pig led to dose-dependent CARPA, while Resovist was reaction-free. Using nanoparticle tracking analysis, it was further determined that Sinerem, more than Resovist, displayed multimodal size distribution and significant fraction of aggregates – factors which are known to promote C activation and CARPA. Taken together, our findings offer physicochemical insight into how key compositional factors and nanoparticle size distribution affect SPION-induced CARPA, a knowledge that could lead to the development of SPIONs with improved safety profiles.

Polymer-coated superparamagnetic iron oxide nanoparticles as T2 contrast agent for MRI and their uptake in liver.

Aim:To study the efficiency of multifunctional polymer-based superparamagnetic iron oxide nanoparticles (bioferrofluids) as a T2 magnetic resonance contrast agent and their uptake and toxicity in liver.Materials & methods:Mice were intravenously injected with bioferrofluids and Endorem®. The magnetic resonance efficiency, uptake and in vivo toxicity were investigated by means of magnetic resonance imaging (MRI) and histological techniques.Results:Bioferrofluids are a good T2 contrast agent with a higher r2/r1 ratio than Endorem. Bioferrofluids have a shorter blood circulation time and persist in liver for longer time period compared with Endorem. Both bioferrofluids and Endorem do not generate any noticeable histological lesions in liver over a period of 60 days post-injection.Conclusion:Our bioferrofluids are powerful diagnostic tool without any observed toxicity over a period of 60 days post-injection.

A novel method for preparation of bare and poly(vinylpyrrolidone) coated superparamagnetic iron oxide nanoparticles for biomedical applications

Pure crystalline superparamagnetic iron oxide nanoparticles (SPIONs) of magnetite (Fe3O4) were prepared from an additive-free aqueous solution of iron(III) nitrate salt though a novel one-pot electrodeposition method. The prepared nanoparticles were characterized by XRD, IR and TEM. The SPIONs were further coated by poly(N-vinyl-2-pyrrolidone) during their deposition process. The coating of PVP on SPIONs was confirmed by FT-IR, DSC-TGA and DLS analyses. The proposed electrochemical route can be concluded as a great routine for the preparation of polymer-coated SPIONs for biomedical applications.

Quantitative Activity Measurements of Brown Adipose Tissue at 7 T Magnetic Resonance Imaging After Application of Triglyceride-Rich Lipoprotein 59Fe-Superparamagnetic Iron Oxide Nanoparticle: Intravenous Versus Intraperitoneal Approach.

The aim of this study was to determine metabolic activity of brown adipose tissue (BAT) with in vivo magnetic resonance imaging (MRI) after intravenous (IV) and intraperitoneal (IP) injection of radioactively labeled superparamagnetic iron oxide nanoparticles (SPIOs) embedded into a lipoprotein layer. Fe-labeled SPIOs were either polymer-coated or embedded into the lipid core of triglyceride-rich lipoproteins (TRL-Fe-SPIOs). First biodistribution and blood half time analysis in thermoneutral mice after IP injection of either TRL-Fe-SPIOs or polymer-coated Fe-SPIOs (n = 3) were performed. In the next step, cold-exposed (24 hours), BAT-activated mice (n = 10), and control thermoneutral mice (n = 10) were starved for 4 hours before IP (n = 10) or IV (n = 10) injection of TRL-Fe-SPIOs. In vivo MRI was performed before and 24 hours after the application of the particles at a 7 T small animal MRI scanner using a T2*-weighted multiecho gradient echo sequence. R2* and ΔR2* were estimated in the liver, BAT, and muscle. The biodistribution of polymer-coated Fe-SPIOs and TRL-Fe-SPIOs was analyzed ex vivo using a sensitive, large-volume Hamburg whole-body radioactive counter. The amount of Fe-SPIOs in the liver, BAT, and muscle was correlated with the MRI measurements using the Pearson correlation coefficient. Tissue uptake of Fe-SPIOs was confirmed by histological and transmission electron microscopy analyses. Triglyceride-rich lipoprotein Fe-SPIOs exhibited a higher blood concentration after IP injection (10.1% ± 0.91% after 24 hours) and a greater [INCREMENT]R2* in the liver (103 ± 5.0 s), while polymer-coated SPIOs did not increase substantially in the blood stream (0.19% ± 0.01% after 24 hours; P < 0.001) and the liver (57 ± 4.08 s; P < 0.001). In BAT activity studies, significantly higher uptake of TRL-Fe-SPIOs was detected in the BAT of cold-exposed mice, with [INCREMENT]R2* of 107 ± 5.5 s after IV application (control mice: [INCREMENT]R2* of 22 ± 5.8 s; P < 0.001) and 45 ± 5.5 s after IP application (control mice: [INCREMENT]R2* of 11 ± 2.9 s; P < 0.01). Fe radioactivity measurements and [INCREMENT]R2* values correlated strongly in BAT (r > 0.85; P < 0.001) and liver tissue (r > 0.85; P < 0.001). Histological and transmission electron microscopy analyses confirmed the uptake of TRL-Fe-SPIOs within the liver and BAT for both application approaches. Triglyceride-rich lipoprotein-embedded SPIOs were able to escape the abdominal cavity barrier, whereas polymer-coated SPIOs did not increase substantially in the blood stream. Brown adipose tissue activity can be determined via MRI using TRL-Fe-SPIOs. The quantification of [INCREMENT]R2* using TRL-Fe-SPIOs is feasible and may serve as a noninvasive tool for the quantitative estimation of BAT activity.

Aggregation of superparamagnetic iron oxide nanoparticles in dilute aqueous dispersions: Effect of coating by double-hydrophilic block polyelectrolyte

Abstract Polymer-coated superparamagnetic iron oxide nanoparticles (SPION) in aqueous dispersion were prepared by the coassembly of SPION coated by an oleate bilayer with the double hydrophilic block polyelectrolyte poly[(3,5-bis(trimethylammoniummethyl)-4-hydroxystyrene iodide]- block -poly(ethylene oxide) (QNPHOS-PEO) and characterized by TEM and AFM. It was found that the coating by QNPHOS-PEO affects their aggregation into larger structures on the micrometer length scale observed by small-angle light scattering as well as the dynamics of the dispersion observed by dynamic light scattering. Oleate-SPION in aqueous dispersions form compact aggregates with the fractal dimension, D = 2.4, and the characteristic size about 2 μm which exhibit internal dynamics manifesting itself by the presence of the relaxation mode with τ ∼ q −3 . In the case of QNPHOS-PEO/oleate-SPION dispersions, the polyelectrolyte coating promotes the formation of compact clusters with the size of the order of ∼10 2 nm. The clusters, weakly interacting by magnetic dipolar interactions, form linear chainlike aggregates with the low fractal dimension, D = 1.2. The dynamics of the QNPHOS-PEO/oleate-SPION dispersions observed by DLS is dominated by the diffusion of the clusters.

Polymer-Coated Superparamagnetic Iron Oxide Nanoparticles: Synthesis, Characterization and Toxicity Evaluation for MRI in Mice

Polymer-Coated Superparamagnetic Iron Oxide Nanoparticles: Synthesis, Characterization and Toxicity Evaluation for MRI in Mice

Biodistribution of newly synthesized PHEA-based polymer-coated SPION in Sprague Dawley rats as magnetic resonance contrast agent

ObjectivesThe purpose of this study was to observe the pharmacokinetic behavior of newly synthesized biocompatible polymers based on polyhydroxyethylaspartamide (PHEA) to be used to coat an iron oxide core to make superparamagnetic iron oxide nanoparticles (SPION).Materials and methodsThe isotopes [14C] and [59Fe] were used to label the polymer backbone (CLS) and iron oxide core (FLS), respectively. In addition, unradiolabeled cold superparamagnetic iron oxide nanoparticles (SPION/ULS) were synthesized to characterize particle size by dynamic light scattering, morphology by transmission electron microscopy, and in vivo magnetic resonance imaging (MRI). CLS and FLS were used separately to investigate the behavior of both the synthesized polymer and [Fe] in Sprague Dawley (SD) rats, respectively. Because radioactivity of the isotopes was different by β for CLS and γ for FLS, synthesis of the samples had to be separately prepared.ResultsThe mean particle size of the ULS was 66.1 nm, and the biodistribution of CLS concentrations in various organs, in rank order of magnitude, was liver > kidney > small intestine > other. The biodistribution of FLS concentrations was liver > spleen > lung > other. These rank orders show that synthesized SPION mainly accumulates in the liver. The differences in the distribution were caused by the SPION metabolism. Radiolabeled polymer was metabolized by the kidney and excreted mainly in the urine; [59Fe] was recycled for erythrocyte production in the spleen and excreted mainly in the feces. The MR image of the liver after intravenous injection demonstrated that [Fe] effectively accumulated in the liver and exhibited high-contrast enhancement on T2-weighted images.ConclusionThis newly synthesized, polymer-coated SPION appears to be a promising candidate for use as a liver-targeted, biocompatible iron oxide MR imaging agent.

A screening paradigm for the design of improved polymer-coated superparamagnetic iron oxide nanoparticles

Polymer-coated superparamagnetic iron oxide nanoparticles (NPs) have been used for a variety of biomedical applications, including as MRI contrast agents, for the treatment of iron anemias, and for ex vivo labeling of the cells used in cell-based therapies so that they can be tracked by MRI. Here we describe a three-stage screening paradigm to develop high potency (i.e., high relaxivity), stable, polymer-coated superparamagnetic iron oxide NPs. Each screen examined different facets of the interaction between iron oxides and polymers. First, an Ion Challenge Screen assessed whether a polymer interacted with the surface of the iron oxide. Second, a Synthesis Optimization Screen examined whether polymers that passed the Ion Challenge Screen were compatible with the synthetic method used to make NPs, and optimized the synthetic method for each polymer. Finally, a Heat Stress/Stability Screen assessed the stability of the optimized polymer-coated superparamagnetic iron oxides that passed the Synthesis Optimization Screen. A carboxymethyl dextran-coated superparamagnetic iron oxide nanoparticle (CMD-NP) with a transverse relaxivity (R2) of 271 mM−1 s−1 and a diameter of 47 nm by dynamic light scattering was obtained. A second NP, a carboxymethyl polyvinyl alcohol-coated nanoparticle (CMPVA-NP) had an R2 of 119 and diameter of 37 nm, but was less stable to heat stress than the CMD-NP. The CMD-NP is a polymer-coated superparamagnetic iron oxide NP with improved relaxivity and high stability achieved without the crosslinking procedure used in our cross-linked iron oxide (CLIO) NP.

Antibiofouling amphiphilic polymer-coated superparamagnetic iron oxide nanoparticles: synthesis, characterization, and use in cancer imaging in vivo

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used as T2-contrast agents for magnetic resonance imaging (MRI). Herein we develop various antibiofouling amphiphilic polymer-coated SPIONs using a one-step nanoemulsion method. This methodology yielded ultrasmall polymer-coated SPIONs, of average diameter less than 30 nm, which were stable under physiological conditions. In vitrocell cytotoxicity tests revealed that no SPION showed toxicity even at relatively high concentrations. In vivo MRI with Lewis lung carcinoma (LLC) tumor-bearing mice resulted in an approximately 30% T2 signal drop in tumor tissues, indicating that the SPIONs reached such tissues via passive targeting. In summary, the ultrasmall, stable, amphiphilic polymer-coated SPIONs can be used as MRI contrast agents for cancer imaging.

Antibiofouling Polymer-Coated Superparamagnetic Iron Oxide Nanoparticles as Potential Magnetic Resonance Contrast Agents for in Vivo Cancer Imaging

We report the fabrication and characterization of antifouling polymer-coated magnetic nanoparticles as nanoprobes for magnetic resonance (MR) contrast agents. Magnetite superparamagnetic iron oxide nanoparticles (SPION) were coated with the protein- or cell-resistant polymer, poly(TMSMA-r-PEGMA), to generate stable, protein-resistant MR probes. Coated magnetic nanoparticles synthesized using two different preparation methods (in situ and stepwise, respectively) were both well dispersed in PBS buffer at a variety of pH conditions (pH 1-10). In addition, dynamic light scattering data revealed that their sizes were not altered even after 24 h of incubation in 10% serum containing cell culture medium, indicative of a lack of protein adsorption on their surfaces. When the antibiofouling polymer-coated SPION were incubated with macrophage cells, uptake was significantly lower in comparison to that of the popular contrast agent, Feridex I.V., suggesting that the polymer-coated SPION can be long-circulated in plasma by escaping from uptake by the reticular endothelial system (RES) such as macrophages. Indeed, when the coated SPION were administered to tumor xenograft mice by intravenous injection, the tumor could be detected in T2-weighted MR images within 1 h as a result of the accumulation of the nanomagnets within the tumor site. Although the poly(TMSMA-r-PEGMA)-coated SPION do not have any targeting ligands on their surface, they are potentially useful for cancer diagnosis in vivo.