Ferrocene Modified Oxidized Dextran Micelles for Anti-Cancer Drug Delivery

A novel amphiphilic polymer carrier named Fe-ODex was successfully synthesized by modifying ferrocene (Fe) groups onto oxidized dextran (ODex) via a Schiff base reaction, endowing it with the ability to induce Fenton reactions. This amphiphilic polymer enables self-assembly into micelles, making it a promising drug delivery system. Using doxorubicin (DOX) as a model anticancer drug, the DOX-loaded micelles Fe-ODex@DOX were prepared through the dialysis method, and the self-assembly properties, pH responsiveness, and cytotoxicity of micelles were systematically investigated. The results confirm that Fe-ODex exhibits excellent performance in multiple aspects. Its amphiphilic structure allows stable self-assembly into micelles, ensuring effective encapsulation and protection of DOX during circulation. Cytotoxicity tests reveal that the blank Fe-ODex carrier has low toxicity with a cell survival rate exceeding 87%, indicating good biocompatibility. Collectively, Fe-ODex integrates pH-triggered drug release, Fenton reaction-mediated oxidative therapy, and biocompatibility, presenting a potential synergistic strategy for targeted cancer treatment. Importantly, the polymer shows remarkable pH responsiveness due to the presence of imine bonds formed via the Schiff base reaction. The drug-loaded micelles achieve a DOX release of 69% after 108 h at pH 5.0. In the slightly acidic microenvironment of tumors (pH 5.0–6.5), these imine bonds break, triggering the disassembly of Fe-Dex@DOX micelles and rapid release of DOX, which directly kills cancer cells while reducing damage to normal tissues. Additionally, Fe-ODex demonstrates strong Fenton reaction-inducing activity. Tumor cells, characterized by high metabolism, produce excessive hydrogen peroxide (H₂O₂). The ferrocene groups in the carrier react with this endogenous H₂O₂ through the Fenton reaction, generating highly cytotoxic hydroxyl radicals (·OH). These radicals further induce oxidative damage to tumor cells, including DNA breakage and lipid peroxidation, synergizing with DOX to enhance anticancer efficacy.