Red Blood Cell Membrane‐Camouflaged Red Phosphorus‐Modified C₃N₄ for Enhanced Tumoral Photodynamic Therapy

Abstract The clinical application of photodynamic therapy (PDT) faces limitations due to the poor tumor‐targeting efficiency and systemic toxicity of conventional photosensitizers. To overcome these challenges, a biomimetic nanoplatform (C3N4‐RP@RBCm) is developed by covalently coupling graphitic carbon nitride (C3N4) with red phosphorus nanoparticles, followed by encapsulation with erythrocyte membranes. This design utilizes CD47‐mediated immune evasion and achieves tumor‐specific accumulation through enhanced permeability and retention (EPR) effects. C3N4‐RP@RBCm demonstrates outstanding antitumor activity. Specifically, a 24‐h exposure to 20 µg mL −1 of C3N4‐RP@RBCm is sufficient to saturate HeLa cells. Upon 660 nm laser irradiation, controlled reactive oxygen species (ROS) are generated, resulting in apoptosis in 89% of HeLa cells, thereby efficiently enhancing anti‐tumor effects. In tumor‐bearing mice, laser‐activated C3N4‐RP@RBCm induces apoptosis in tumor cells and more effectively inhibits tumor xenografts. Moreover, at a concentration of 100 µg mL −1 , the percentage of live cells remains above 99%, and the treatment induces less than 1.2% hemolysis in human erythrocytes, indicating excellent biocompatibility. Consequently, C3N4‐RP@RBCm causes minimal histopathological injuries in heart, liver, spleen, lung, and kidney tissues. Thus, this photosensitizer demonstrates significant potential for clinical application.