A tumor microenvironment-responsive microneedle patch for chemodynamic therapy of oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors of the head and neck, and this disease has become a threat to public health due to its poor prognosis and high fatality rate. Chemodynamic therapy (CDT) is an emerging oncology treatment based on the Fenton reaction. However, the lack of endogenous hydrogen peroxide (H2O2) in tumor cells and the high concentration of glutathione (GSH) that depletes toxic hydroxyl radicals (<middle dot>OH) significantly impair the efficacy of CDT. Here, we developed a polyvinyl alcohol (PVA)-based soluble microneedle patch (denoted as Fe3O4 + VC-MN) loaded with Fe3O4 nanoparticles (NPs) and vitamin C (VC) for the effective treatment of OSCC. When Fe3O4 + VC-MNs are inserted into the OSCC tissue, the Fe3O4 NPs and VC loaded in the tip of the needle are released in a targeted manner. After VC is converted into oxidized vitamin C (DHA), it can consume GSH in tumor cells and generate sufficient intracellular H2O2 in situ. Moreover, by virtue of their peroxidase-like activity, Fe3O4 NPs can induce the generation of lethal <middle dot>OH through the Fenton reaction with the aforementioned H2O2, leading to tumor cell ferroptosis and apoptosis, thus achieving CDT. Collectively, this functional microneedle patch provides a more efficient and minimally invasive targeted drug delivery solution for the treatment of OSCC.