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 (MnO 2 ) layer on a porphyrinic MOF core, followed by conjugation with PD‐L1‐targeting aptamers. Upon reaching the tumor, the MnO 2 shell scavenges glutathione (GSH) while concurrently releasing O 2 for hypoxia alleviation and Mn 2+ 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.