Enhancing Physicochemical Properties and Biocompatibility of Hollow Porous Iron Oxide Nanoparticles through Polymer-Based Surface Modifications

In this study, we synthesized hollow porous iron oxide nanoparticles (HPIONPs) with surface modifications using polymers, specifically chitosan (Chi), polyethylene glycol (PEG), and alginate (Alg), to improve colloidal stability and biocompatibility. For colloidal stability, Alg-coated HPIONPs maintained size stability up to 24 h, with only an 18% increase, while Chi, PEG, and uncoated HPIONPs showed larger size increases ranging from 64 to 140%. The biocompatibility of polymer-coated HPIONPs was evaluated by assessing their cell viability, genotoxicity, and hemocompatibility. Across tested concentrations from 6.25 to 100 μg/mL, both uncoated and polymer-coated HPIONPs showed minimal cytotoxicity against three normal cell lines: RAW264.7, 3T3-L1, and MCF10A, with cell viability exceeding 80% at the highest concentration. Notably, polymer-coated HPIONPs exhibited nongenotoxicity based on the micronucleus assay and showed hemocompatibility, with only 2–3% hemolysis in mouse blood, in contrast to uncoated HPIONPs which exhibited 4–5%. Furthermore, we evaluated the cytotoxicity of HPIONPs on MDA-MB-231 breast cancer cells after a 2 h exposure to a stationary magnetic field, and the results showed the highest cell death of 38 and 29% when treated with uncoated and polymer-coated HPIONPs at 100 μg/mL, respectively. This phenomenon is attributed to iron catalyzing the Fenton and Haber-Weiss reactions, leading to reactive oxygen species (ROS)-dependent cell death (r ≥ 0.98). In conclusion, the hydrothermal synthesis and subsequent surface modification of HPIONPs with polymers showed improved colloidal stability, nongenotoxicity, and hemocompatibility compared to uncoated HPIONPs while maintaining closely similar levels of cytotoxicity against both normal and cancer cells. This research has paved the way for further exploration of polymer coatings to enhance the overall performance and safety profile of magnetic nanoparticles in delivering anticancer drugs.