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

Abstract

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 (·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 H₂O₂in situ. Moreover, by virtue of their peroxidase-like activity, Fe₃O₄ NPs can induce the generation of lethal ·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.