Zein-Based Nanomedicines for Synergistic Chemodynamic/Photodynamic Therapy

Current cancer treatment is not only limited to monotherapy but is also influenced by limited drug delivery options. Combined chemokinetic-photokinetic therapy has great promise in enhancing anticancer effects. Meanwhile, zein has superior self-assembly properties and can be loaded with photosensitizers. Herein, the targeted multifunctional nanoparticles based on zein/hyaluronate acid (HA)/tannin (TA)/Cu²⁺ loaded with IR780 (ZHTC@IR780) are constructed for synergetic cancer therapy by chemo-dynamic therapy (CDT) and photodynamic therapy (PDT). There is experimental proof that ZHTC@IR780 nanoparticles (NPs) can relieve the tumor hypoxic microenvironment by catalytic decomposition of endogenous H₂O₂ to O₂ and further react with O₂ to produce toxic ¹O₂ with 808 nm laser irradiation. The glutathione oxidase-like effects of ZHTC@IR780 NPs can generate Fenton-like Cu⁺ ions and deplete GSH for efficient hydroxyl radical (^•OH) production. In addition, CDT combined with PDT enhances the antitumor effect. Photodynamic therapy can cause immunogenic cell death, increase calreticulin eversion, release histone with high mobility, and promote apoptosis of tumor cells.