Photothermal-Triggered\nExtracellular Matrix Clearance\nand Dendritic Cell Maturation for Enhanced Osteosarcoma Immunotherapy

Osteosarcoma, a predominant malignant tumor among adolescents,\nexhibits high mortality and suboptimal immunotherapy efficacy due\nto a collagen-dense extracellular matrix (ECM) that hinders cytotoxic\nT lymphocyte (CTL) infiltration. Herein, we developed mesoporous polydopamine\n(MPDA) nanoparticles encapsulating bromelain and the immune adjuvant\nR848 (M@B/R), aimed at enhancing photothermal immunotherapy. These\nnanoparticles efficiently accumulate at the tumor site following injection.\nUpon near-infrared (NIR) light irradiation, photothermal therapy (PTT)\ninduces immunogenic cell death in tumor cells and, with the aid of\nR848, efficiently promotes dendritic cell maturation, activating antitumor\nimmunity and leading to CTL infiltration into the tumor. Concurrently,\nNIR-induced heating activates bromelain, resulting in ECM degradation\nand improved CTL penetration into the tumor. Our <i>in vivo</i> evaluations demonstrate potent antitumor effects in osteosarcoma-bearing\nmice. This integrated approach offers a promising strategy for overcoming\nphysical barriers in ECM-rich tumors, marking a significant advancement\nin the treatment of osteosarcoma.