Enantioselective Induction of Immunogenic Cell Death: A Type-I Photodynamic Therapy Enabled by Chiral Porphyrin/Arginine Self-Assemblies

. This chiral signature translates to significant biological enantioselectivity. d-Arg-TPPS achieves 3.87-fold greater cellular uptake and 1.85-fold higher intracellular reactive oxygen species (ROS) production than l-Arg-TPPS, resulting in markedly enhanced chirality-specific antitumor activity. Importantly, l/d-Arg-TPPS also elicits a chirality-dependent immunogenic cell death (ICD) response, facilitating antitumor immunity. This work establishes a supramolecular chiral-engineering strategy that integrates hypoxia-tolerant photodynamic behavior with stereoselective nanobio interactions, advancing both the fundamental understanding and therapeutic potential of photosensitizer design.