A pH-Responsive Charge-Reversal Nanoplatform for Combined Chemophotothermal Therapy of Oral Cancer

Abstract The global incidence of oral cancer has risen rapidly at progressively younger ages due to the impact of unhealthy lifestyle habits. Therefore, there is an urgent need to develop novel oral cancer treatments. Combination therapy with chemotherapy and photothermal therapy offers a superior therapeutic effect compared to conventional clinical methods. Herein, we report the development of a pH-responsive and charge-reversal nanomedicine system to enhance oral cancer therapy. Polydopamine (PDA), known for its excellent photothermal properties, was initially coated onto a copolymer PLGA loaded with the chemotherapeutic drug DOX. Subsequently, poly(2-ethyl-2-oxazoline) (PEOz) was employed for its surface modification. This charge-reversal system, equipped with a tertiary amide group on the main chain, ensures that the nanoparticles remain negatively charged during blood circulation and become positively charged at the tumor site under weakly acidic conditions. The results suggest that the nanoplatform system exhibits outstanding photothermal performance and controlled DOX release. Both in vitro and in vivo experiments have demonstrated that this drug delivery system exhibits excellent antitumor efficacy and biosafety. This study has significant implications for the clinical treatment of oral cancer.