A Microneedle Patch with Self-Oxygenation and Glutathione Depletion for Repeatable Photodynamic Therapy

Photodynamic therapy (PDT) has attained extensive attention as a noninvasive tumor treatment modality. However, the hypoxia in solid tumors, skin phototoxicity of "always on" photosensitizers (PSs), and abundant supply of glutathione (GSH) in cancer cells severely hampered the clinical applications of PDT. Herein, a self-oxygenation nanoplatform (denoted as CZCH) with GSH depletion ability was encapsulated into the hyaluronic acid microneedle patch (MN-CZCH) to simultaneously improve the biosafety and therapeutic efficacy of PDT. The Cu²⁺-doped porous zeolitic imidazolate framework incorporated with catalase (CAT) is capable of efficiently loading PS 2-(1-hexyloxyethyl)-2-divinylpyropheophorbic-a (HPPH). The CZCH intermingled MN patch (MN-CZCH) could effectively penetrate the stratum corneum, topically transport HPPH to the target tumor site, achieve a long tumor retention time, and enhance the efficacy of PDT via the simultaneously synergistic effect of CAT-catalyzed self-supplying O₂ and Cu²⁺-mediated GSH depletion. Using traceable fluorescence (FL) imaging of the released HPPH from CZCH, the FL imaging-guided repeatable PDT can be achieved for enhanced antitumor efficacy. As a result, the MN-CZCH patch exhibited excellent therapeutic efficacy against melanoma with minimal toxicity, which has promising potential for cancer theranostics.