A ferroptosis-targeting detachable dissolvable microneedle as a combined therapeutic strategy for radiation-induced oral mucositis

Radiation-induced oral mucositis (RIOM) is a common complication among patients undergoing radiotherapy. Ionizing radiation (IR) has been shown to induce the excessive production of reactive oxygen species (ROS) and ferroptosis, both of which play critical roles in the development of RIOM. This study fabricates a novel detachable dissolvable microneedle patch DC@MNs for the therapy of RIOM. The nano-enzyme Ceria nanoparticles (Ceria NPs) at the top of needle tips can scavenge ROS and enhance penetration capability of DC@MNs. Additionally, the microneedles (MNs) incorporate deferoxamine (DFO), a known ferroptosis inhibitor, to form a combined therapeutic strategy for RIOM. Cell viability assays demonstrate that the combination of DFO and Ceria NPs effectively mitigates IR-induced cell death. Furthermore, in vivo studies using rat RIOM models further confirm that DC@MNs can penetrate the mucosal epithelium, thereby facilitating drug delivery. Finally, measurement of intracellular ROS, lipid peroxidation, and ferrous ion levels reveals that the DC@MNs protect oral mucosal cell through ROS scavenging and ferroptosis inhibition. This study provides a novel radiation protection strategy and highlights its potential applicability in drug delivery to oral mucosal for patients receiving radiotherapy.