Flexible Microneedle Platform for Synergistic Chemo/Photothermal Ferroptosis Therapy via P-Glycoprotein Inhibition in Breast Cancer

Combining photothermal therapy (PTT) with chemotherapy shows promise for cancer treatment, but its efficacy is limited by heat shock protein (HSP)-induced thermoresistance and P-glycoprotein (P-gp)-mediated drug efflux. To overcome these challenges, we developed a tumor microenvironment-responsive microneedle platform for synergistic chemotherapy, PTT, and ferroptosis in breast cancer. The system employs Fe³⁺-coordinated dihydromyricetin (DMY) nanocarriers encapsulating doxorubicin (DMFD NPs) integrated into a flexible polyvinylpyrrolidone (PVP) microneedle patch. The patch adheres tightly to tumors, enabling the rapid delivery and targeted release of DMFD NPs under laser irradiation and acidic conditions. Released Fe³⁺/Fe²⁺ ions generate reactive oxygen species (ROS) via Fenton reactions, synergizing with PTT to induce ferroptosis. DMY concurrently inhibits HSP and P-gp, enhancing photothermal-chemotherapy efficacy. In vivo, this approach achieved 92% tumor inhibition, demonstrating its potential to address the limitations of conventional PTT and chemotherapy through localized multifunctional action.