Near-Infrared Photothermal-Pyroelectric Coupling (PTPC)-Activated Trace Element Prodrug Nanoplatform for Tumor-Specific Immune Modulation and Therapy

Despite the therapeutic promise of trace elements (TEs), because of their rich biological activity, the clinical translation remains hampered by the poor bioavailability, off-target toxicity, and lack of spatiotemporal control. Here, we propose a novel photoactivated TEs prodrug therapy (TEPT), leveraging a selenium-doped black phosphorus (Se-BP) nanoplatform that integrates photothermal-pyroelectric coupling (PTPC) for precise tumor targeting and immune activation. Synthesized via a scalable chemical vapor transport (CVT) process, Se atoms are seamlessly incorporated into the BP lattice. Upon pulsed near-infrared (NIR) laser irradiation, Se-BP converts a thermal pulse into pyroelectric current, triggering localized reactive oxygen species (ROS) generation to drive spatiotemporally controlled Se release. The liberated Se is subsequently oxidized to cytotoxic selenite, selectively inducing cancer cell apoptosis. Concurrently, Se reprograms the tumor immune microenvironment (TIME) and sensitizes the immune checkpoint blockade (ICB). This work offers a modular and biodegradable 2D prodrug platform with broad translational potential across oncology and beyond.