Drug-Loaded Polymer-Coated Graphitic Carbon Nanocages for Highly Efficient in Vivo Near-Infrared Laser-Induced Synergistic Therapy through Enhancing Initial Temperature

Abstract

Graphitic carbon nanocages (GCNCs) have unique geometric structures and physical properties, which have been extensively investigated for various applications. However, no reports focusing on using GCNCs and polymer-coated GCNCs for solid tumor ablation induced by near-infrared laser irradiation under enhanced initial body temperature, or on the biosafety of GCNCs in vivo, have been published. Here, we developed chitosan (CS)-coated GCNCs and showed that both GCNCs and GCNCs/CS in mouse tumors can rapidly convert an 808 nm laser light energy into heat, which efficiently kill nasopharyngeal carcinoma cells and inhibit tumor growth. The tumors are further damaged by the phototoxicity of GCNCs/CS after loading with 5-Fluorouracil (5FU). Tumors are no longer detected after 6 days of 5FU-GCNCs/CS treatment under irradiation, which is due to the synergistic effect of the photothermal response of GCNCs and the chemotherapy of 5FU. None of the tumors reappeared during the following 12 days of no irradiation. Interestingly, increasing the initial body temperature of the mice significantly improved the photothermal effect of GCNCs in vivo and the synergistic effect of photothermal therapy and chemotherapy, thus accelerating the shrinking of tumors. To the best of our knowledge, this is the first study to improve the photothermal ablation of GCNCs and synergetic photothermal-chemotherapy of drug-loaded GCNCs through enhancing the initial body temperature. As the results show that GCNCs, GCNCs/CS, and 5FU-GCNCs/CS are safe in mice after intratumoral injection both with and without laser irradiation, our technique may have great potential for future clinical translation.