Dual-phase injectable thermosensitive hydrogel incorporating Fe3O4@PDA with pH and NIR triggered drug release for synergistic tumor therapy

Abstract

Synergistic tumor ablation strategies combining photothermal therapy (PTT) and chemotherapy have unique advantages in solving thermal damage and pharmaceutical side effects to normal tissues. An excellent near-infrared (NIR) triggered drug repository system can realize on-demand chemotherapeutic drug release and hyperthermia-assisted apoptosis to combat tumor proliferation. Herein, an injectable thermosensitive hydrogel system CS/HPC/GP-Fe3O4@PDA (Gel) was proposed, which used dual-phase chitosan/hydroxypropyl cellulose (CS/HPC) composite network incorporating polydopamine (PDA) -modified Fe3O4 nanocubes as NIR-responsive carriers, loaded with doxorubicin hydrochloride (DOX), a potent antitumor drug. The dense porous structure of Gels effectively minimized the advance leakage of therapeutic agents and triggered the release of DOX through photothermal conversion, while showing pH and NIR power density dependence. This stimulus-responsive release behavior and high photothermal conversion efficiency from Fe3O4@PDA NCs allowed the simultaneous action of PTT and chemotherapy to efficiently kill tumor cells in vitro. In addition, the Gel system was non-cytotoxic and degraded rapidly upon completion of its therapeutic mission, indicating outstanding potential as a tumor ablation material.