Light/Ultrasound Dual Responsive Carbon Dots‐Based Nanovaccines for Multimodal Activation Tumor Immunotherapy of Melanoma

One braw-new kind of light/US dual-responsive carbon dots (CDs)-based nanovaccines is developed using copper-nitrogen-coordinated CDs composited with ovalbumin. The complementary advantages of phototherapy and sonodynamic therapy enhanced antitumor immunotherapy via multimodal promotion of dendritic cell maturation, including phototherapy-induced immunogenic cell death, US-triggered reactive oxygen species, and model antigen ovalbumin.

Abstract

Melanoma is a highly aggressive and metastatic tumor, and immunotherapy has become the current solution. However, conventional nanovaccines do not strongly activate T cell immune responses. Therefore, development of effective therapeutic nanovaccines to activate systemic antitumor immunity is urgently required. Herein, light/ultrasound (US) dual-responsive carbon dot-based nanovaccines (Cu-N-CDs@OVA) are designed using copper-nitrogen-coordinated carbon dots composited with ovalbumin. Under 650-nm laser irradiation, Cu-N-CDs@OVA exhibited superior photothermal ablation of primary tumors, induced immunogenic cell death and released antigens by phototherapy, facilitating the maturation of dendritic cells (DCs). More importantly, Cu-N-CDs@OVA stably penetrated and diffused upon US treatment, eradicating metastatic tumors and generating low-dose reactive oxygen species to activate DCs. By integrating with the model antigen OVA, the combined multimodal treatment promotes DC maturation to activate systematic antitumor immunity. This is the first example of a light/US dual-responsive therapeutic nanovaccine that provides a paradigm for the production of personalized nanovaccines against malignant tumors.