Microneedle-Mediated "On-Demand" Prodrug Delivery Platform for Precise Superficial Tumor Therapy.

The central paradigm in cancer chemotherapy revolves around expanding the therapeutic window: maximizing antitumor potency while minimizing off-target toxicity. Conventional drug delivery methods for superficial tumors (such as systemic and intratumoral injections) suffer from several limitations, including inefficient drug delivery and off-target toxicity. In contrast, the activated-prodrug strategy can significantly address the drawbacks associated with conventional chemotherapeutic agents. These improvements include reducing systemic toxicity, enhancing tumor targeting, and improving drug solubility, thereby offering transformative perspectives for optimizing conventional chemotherapy. However, current prodrug systems remain constrained by rapid systemic elimination, necessitating frequent administration. Thus, novel strategies need to be developed to enhance prodrug delivery. Microneedles (MNs) represent a promising therapeutic platform for precise and controllable drug delivery, particularly in the management of superficial tumors. In this study, we propose an MN drug delivery system for the transdermal administration of reactive oxygen species (ROS)-activated prodrug (FDOCl-19), facilitating in situ drug delivery and selective chemotherapy. Our results establish that this FDOCl-19-loaded MN (FDOCl-19@MN) elicits tumor cell apoptosis in vitro. In mouse models of subcutaneous melanoma, FDOCl-19@MN significantly promoted tumor regression with minimal systemic toxicity, demonstrating favorable biosafety. Collectively, this work establishes FDOCl-19@MN as a transdermal theranostic platform featuring minimally invasive MNs that deliver ROS-activated prodrugs (FDOCl-19) for spatiotemporally controlled treatment of superficial tumors.