Self-Enhancing Photodynamic / Immunotherapy via a MOF Nanoplatform for Combined STING Activation and Immune Checkpoint Blockade.

Abstract

Combinational photodynamic and immune checkpoint blockade (PDT/ICB) therapy is a promising approach for oncotherapy. However, the tumor microenvironment (TME) poses multiple biological barriers that can critically undermine the treatment outcomes of PDT/ICB. To this end, a cascade-amplified photodynamic immunotherapy nanoplatform based on the core-shell structured metal-organic frameworks (MOFs) was elaborately constructed. This nanoplatform, termed PMA, was constructed by growing manganese oxide (MnO2) layer on a porphyrinic MOF core, followed by conjugation with PD-L1-targeting aptamers. Upon reaching the tumor, the MnO2 shell scavenges glutathione (GSH) while concurrently releasing O2 for hypoxia alleviation and Mn2+ ions as STING agonists. Simultaneously, MOF-based core was directly self-assembled from porphyrin photosensitizers (PSs) and metal clusters, resulting in high PSs loading capacity without self-quenching. More importantly, the liberated PD-L1 aptamers block immune checkpoint interactions, reversing local immunosuppression and activating cytotoxic T lymphocytes. Together, this multimodal strategy evokes robust antitumor immunity, offering a powerful and translatable approach to expand the scope of cancer immunotherapy.