Multifunctional Graphene Oxide Quantum Dot Nanoformulation with Key Immunomodulation for Effective Anticancer Therapy in Mice Model.

INTRODUCTION: To overcome limitations in melanoma therapy by developing a targeted nanoplatform based on reduced graphene oxide quantum dot (rGOQD) that integrates photothermal therapy (PTT), chemodynamic therapy (CDT), and immune modulation. METHODS: The multifunctional rGOQD/MnO(2)/CpG/Q/FA system combines rGOQD for efficient near-infrared (NIR) photothermal conversion efficiency, MnO(2) as a Fenton-like catalyst for hydroxyl radical (•OH) generation, quercetin (Q) to inhibit heat shock protein 70 (HSP70) and enhance PTT sensitivity, and CpG-ODN as a TLR9 agonist for immune activation. Folic acid (FA) enables targeted delivery to folate receptor-overexpressing B16F10 melanoma cells. Comprehensive in vitro and in vivo studies assessed photothermal performance, reactive oxygen species (ROS) generation, macrophage polarization, cytokine release, and anti-tumor efficacy. RESULTS: The nanoplatform exhibited strong PTT/CDT effects, efficient glutathione (GSH) depletion, and enhanced intracellular uptake via FA targeting. It induced apoptosis and immunogenic cell death (ICD) characterized by calreticulin (CRT) exposure and high mobility group protein B1 (HMGB1) release, while promoting macrophage repolarization to the M1 phenotype. In vivo, rGOQD/MnO(2)/CpG/Q/FA combined with near infrared (NIR) irradiation significantly inhibits tumor growth, prolongs survival, and activates systemic immunity without systemic toxicity in mice model. CONCLUSION: This targeted nanoplatform offers a promising strategy to integrate localized PTT/CDT with systemic immune modulation, addressing key limitations of current melanoma therapies.