Electrostatic Force-Enabled Microneedle Patches that Exploit Photoredox Catalysis for Transdermal Phototherapy.

Microneedle patches for topical administration of photodynamic therapy (PDT) sensitizers are attractive owing to their safety, selectivity, and noninvasiveness. However, low-efficiency photosensitizer delivery coupled with the limitations of the hypoxic tumor microenvironment remains challenging. To overcome these issues, we developed an effective microneedle patch based on intermolecular electrostatic interactions within a photosensitizer matrix containing a zinc-containing porphyrin analogue, ZnBP (w). This design improved the mechanical strength of the microneedle patch and enhanced the photosensitizer loading efficiency in aqueous environments. A key feature of the system is efficient electron transfer between ZnBP (w) and NADH upon photoirradiation. Electrostatic interactions between ZnBP (w) and NADH were hypothesized to support initial binding and subsequent photoinduced electron transfer, disrupting NADH/NAD(+) homeostasis and inducing tumor cell death. The developed microneedle patch demonstrated an antiangiogenesis effect in a vascular malformation model and an antitumor effect in a melanoma mouse model after transdermal administration. This study highlights the benefits of electrostatic interactions in designing microneedle PDT patches and their clinical potential, particularly in reducing systemic phototoxicity.