Electrostatic Force-Enabled\nMicroneedle Patches that\nExploit Photoredox Catalysis for Transdermal Phototherapy

Microneedle patches for topical administration of photodynamic\ntherapy (PDT) sensitizers are attractive owing to their safety, selectivity,\nand noninvasiveness. However, low-efficiency photosensitizer delivery\ncoupled with the limitations of the hypoxic tumor microenvironment\nremains challenging. To overcome these issues, we developed an effective\nmicroneedle patch based on intermolecular electrostatic interactions\nwithin a photosensitizer matrix containing a zinc-containing porphyrin\nanalogue, <b>ZnBP (w)</b>. This design improved the mechanical\nstrength of the microneedle patch and enhanced the photosensitizer\nloading efficiency in aqueous environments. A key feature of the system\nis efficient electron transfer between <b>ZnBP (w)</b> and NADH\nupon photoirradiation. Electrostatic interactions between <b>ZnBP\n(w)</b> and NADH were hypothesized to support initial binding and\nsubsequent photoinduced electron transfer, disrupting NADH/NAD<sup>+</sup> homeostasis and inducing tumor cell death. The developed\nmicroneedle patch demonstrated an antiangiogenesis effect in a vascular\nmalformation model and an antitumor effect in a melanoma mouse model\nafter transdermal administration. This study highlights the benefits\nof electrostatic interactions in designing microneedle PDT patches\nand their clinical potential, particularly in reducing systemic phototoxicity.