Nanoparticle-Mediated Explosive Anti-PD-L1 Factory Built in Tumor for Advanced Immunotherapy

Immunotherapy, particularly immune checkpoint blockade (ICB) therapies, has revolutionized oncology. However, it encounters challenges such as inadequate drug accumulation and limited efficacy against "cold" tumors characterized by lack of T cell infiltration and immunosuppressive microenvironments. Here, a controlled antibody production and releasing nanoparticle (CAPRN) is introduced, designed to augment ICB efficacy by facilitating tumor-targeted antibody production and inducing photodynamic cell death. CAPRN achieves tumor-specific accumulation via pH-responsive PEG detachment, enabling efficient intracellular gene delivery encoding anti-PD-L1 antibody. Laser-induced photodynamic therapy (PDT) not only triggers cancer cell death but also facilitates targeted antibody release from dying tumor cells. CAPRN demonstrates significant anti-tumor efficacy, attributed to multiple effects including enhanced antibody release, dendritic cell (DC) maturation, and T cell activation. Moreover, CAPRN exhibits substantial tumor suppression in both primary and bilateral tumor models, accompanied by activated T cell infiltration and enhanced immune responses. This study presents a novel strategy for priming robust immunotherapy, offering targeted antibody release through laser-assisted photodynamic nanoparticles.