Fe₃O₄-Based Multifunctional Nanospheres for Amplified Magnetic Targeting Photothermal Therapy and Fenton Reaction

Multifunctional nanoplatforms have attracted the interests of many scientists because they can achieve better therapeutic effect in the combined treatment of cancer. A novel cancer therapeutic strategy which combines an Fe₃O₄-based in vivo Fenton reaction with polypyrrole (PPy)-based photothermal therapy (PTT) was proposed. The multifunctional nanocomposite was comprised of Fe₃O₄ as the core, PPy as the shell, and polyethylene glycol. PPy could absorb near-infrared (NIR) light strongly and convert it into heat for tumor photothermal ablation, and Fe₃O₄ NPs were used as a target component to guide the nanoparticles to the tumor site under an external magnetic field. It was found that the PPy coating could be used not only for inducing PTT to ablate tumor cells but also for promoting Fe^2+/3+ release from Fe₃O₄ nanoparticles. In vitro cell experiments confirmed that the increased Fe^2+/3+ release could effectively enhance the Fe₃O₄-based Fenton reaction, which catalyzed the conversion of H₂O₂ into a highly toxic hydroxyl radical (^•OH), thus inducing tumor cell apoptosis. Furthermore, our experiments also showed that the PPy coating could generate a photothermal effect to kill 4T1 tumor cells under NIR light exposure but did no harm to normal cells in the dark. Under the guidance of the magnet, we found Fe₃O₄@PPy-PEG (Fe₃O₄@P-P) nanoparticles could effectively enrich in the tumor site, and the therapeutic effect from PTT and the photothermal strengthened Fenton reaction was also verified in vivo. It is confirmed for the first time that the photothermal effect could promote the release of iron ions from Fe₃O₄ under acid conditions and enhance the Fenton reaction. Therefore, the Fe₃O₄@P-P nanoparticles, combined with the Fenton reaction and photothermal effect, and obviously the magnetic targeting and magnetic resonance imaging ability, are able to be a candidate for novel tumor theranostic agents.