Mild-Sunlight-Activated Safe Photodynamic Therapy Using On-Off Polymer Photosensitizers in Wearable Microneedle Patch.

Abstract

Photodynamic therapy (PDT) is promising but limited by its dependence on specialized photosources, clinic-based administration, and prolonged post-treatment light avoidance due to phototoxicity side effects. Here, we report mild-sunlight-activated PDT (SunPDT) microneedle patches incorporating polymeric photosensitizers with an intrinsic "on-off" reactive oxygen species (ROS)-generating mechanism, enabling bio-safe, deep-tissue, and self-administered PDT without fixed clinic visits and strictly prolonged light avoidance post-treatment. Rationally designed photosensitizers generate robust ROS under low-intensity mild sunlight (12 mW cm^-2) excitation, and feature an intrinsic "on-off" ROS generation mechanism that confines ROS generation to lesions, even when photosensitizers diffuse into surrounding healthy tissues. Microneedle-enabled deep photosensitizer delivery and excitation by the near-infrared component of sunlight together allow self-administered treatment of deep-seated lesions without scheduled clinic visits. Importantly, the SunPDT patch's triple-safety design, low-intensity mild sunlight excitation, local delivery of photosensitizer by microneedles, and an intrinsic "on-off" ROS generation mechanism, eliminate post-treatment prolonged light avoidance, ensuring bio-safe PDT. Using female psoriatic mice as a proof-of-concept model, our "on-off" SunPDT microneedle patches achieve high therapeutic efficacy and patient-friendly, self-administered treatment, and outperform clinical Protoporphyrin IX patches, which demonstrate weaker effects and require prolonged light shielding. Therefore, this study establishes a promising design for a lifestyle-integrated PDT platform.