Synergistically Promoted Antitumor Photoimmunotherapy Using Immune-Stimulating Peach Gum Polysaccharides as Nanocarriers

Nanomaterial-based mild photothermal therapy (mPTT, 42-45 °C) with controllable light-triggered thermal diffusion holds potential in reversing immunosuppressive microenvironments and activating antitumor immunity in tumors. However, the limited antitumor efficacy of mPTT alone always requires sophisticated synergistic strategies to promote its overall therapeutic outcome. Herein, we employ an immune-active natural polymer, peach gum polysaccharide (PGP), as the nanocarrier to encapsulate the photothermal reagent of TTQPL to yield PLA-T nanoparticles (NPs). We demonstrate the capability of a PGP-based encapsulation matrix in stimulating the polarization of M0/M2-like macrophages to the pro-inflammatory M1 phenotype. Under NIR light irradiation, PLA-T NPs induce profound apoptosis of CT26 cells by a mitochondrial pathway, which leads to upregulated Bax, downregulated Bcl-2, and released cytochrome C (Cyt C) from the mitochondria to the cytoplasm. Additionally, such a formulation synergistically exploits the intrinsic immunoregulatory function of PGP and NIR light-triggered mPTT, showing superior in vivo antitumor effects by evoking the adaptive immune response with a reversed immunosuppressive tumor microenvironment. In summary, this work highlights the potential of PGP as a natural polymer carrier to deliver therapeutic reagents, offering synergistically enhanced immune activation with superior antitumor performance of phototherapy.