Conformation-gated supramolecular photosensitizer nanoparticles for reversibly switchable photodynamic antibacterial therapy.

Abstract

Photodynamic antibacterial therapy provides an attractive strategy for combating bacterial infections, however, the constitutive activity of photosensitizers often causes nonspecific reactive oxygen species (ROS) generation, compromising spatiotemporal precision and biosafety. Herein, we report a photoresponsive supramolecular co-assembly that enables reversible gating of photodynamic antibacterial activity through light-controlled structural reconfiguration. A cationic porphyrin (TMPyP) and an anionic azobenzene (Azo) derivative spontaneously co-assemble via non-covalent interactions to form supramolecular nanoparticles, in which the porphyrin photosensitizer is maintained in a photodynamically inactive (OFF) state. Upon UV-induced trans-to-cis photoisomerization of Azo, the co-assembly undergoes structural reconstruction, leading to recovery of the porphyrin photodynamic response and restoration of singlet oxygen (1O2) generation under the corresponding irradiation protocol. Consequently, the co-assembly exhibits light-controlled antibacterial activity, showing minimal bactericidal effect in the OFF state but efficient photodynamic killing after activation, accompanied by enhanced intracellular ROS generation and membrane damage. The photoactivated system further accelerates the healing of bacteria-infected wounds in vivo while maintaining excellent hemocompatibility and biocompatibility. This work demonstrates that photoisomerization-mediated supramolecular reconstruction provides an effective strategy for reversibly gating photosensitizer activity, offering a general approach toward spatiotemporally programmable photodynamic antibacterial materials.