Platinum nanozyme co-loaded reactive oxygen species-responsive prodrug integrated with dissolvable microneedle for chemotherapy and photodynamic therapy of melanoma

Abstract

Melanoma, the most aggressive form of skin cancer, is characterized by an increasing incidence rate. However, conventional treatment methods such as surgery, chemotherapy, radiotherapy, and immunotherapy have limitations that hinder their widespread application. In this study, we aim to develop a platinum nanozyme (PtNP) co-loaded reactive oxygen species (ROS)-responsive prodrug integrated with dissolvable microneedle for chemotherapy and photodynamic therapy of melanoma. The utilization of microneedle can significantly enhance the efficiency of transdermal drug delivery while improving treatment efficacy and minimizing toxic side effects. The nanodrug system incorporates a prodrug composed of chemotherapeutic agent, photosensitizer, and ROS-responsive chemical bond. Upon laser irradiation, it generates ROS for effective photodynamic therapy while precisely controlling the release behavior of camptothecin (CPT) within the prodrug formulation. Furthermore, PtNP in the nanodrug exhibits nanozyme-like activity by catalyzing the decomposition of hydrogen peroxide into oxygen to overcome hypoxia-related challenges and enhance the effectiveness of photodynamic therapy. The integration of the nanodrug complex with dissolvable microneedle presents a synergistic approach for the combined delivery of chemotherapy and photodynamic therapy to melanoma patients, offering novel strategies and avenues for clinical treatment.