Activatable Enzyme-Photosensitizer Nano-Assembly Incorporated into Microneedle Patch for Self-Oxygenating Photodynamic Therapy

Photodynamic therapy (PDT) faces challenges like limited photosensitizer (PS) bioavailability and inadequate oxygen supply. Herein, we have developed an activatable catalase (CAT)-PS nano-assembly incorporated into a microneedle (MN) patch for self-oxygenating PDT. CAT serves as a versatile carrier to deliver multiple hydrophobic PSs, and the MN patch enhances the efficiency of local delivery. We found that CAT can interact with various hydrophobic PSs, self-assembling into homogeneous and stable PS@CAT nanoparticles (NPs). The binding of these hydrophobic PSs to the hydrophobic pocket of CAT within the NPs suppresses its catalytic activity. The MN patch delivers PS@CAT NPs to tumor tissues, where acidity triggers PS release. CAT also consumes H2O2 in the tumor microenvironment to produce O2, alleviating hypoxia. In vivo tests show this approach safely and effectively inhibits 4T1 murine mammary carcinoma growth, presenting a novel PDT strategy for cancer treatment.