Biocompatible Chitosan-Carbon Nanocage Hybrids for Sustained Drug Release and Highly Efficient Laser and Microwave Co-irradiation Induced Cancer Therapy

摘要： Graphitic carbon nanocages (GCNCs) are unique graphene-based nanomaterials that can be used for cancer photothermal therapy (PTT). However, low toxicity GCNC-based organic/inorganic hybrid biomaterials for microwave irradiation assisted PTT have not yet been reported. In the present study, chitosan (CS)-coated GCNCs (CS-GCNCs) loaded with 5-fluorouracil (5Fu) were used for cancer therapy when activated by 808-nm laser and microwave co-irradiation. The cytotoxicity of GCNCs was significantly reduced after coating with CS. For example, fewer cell-cycle defects were caused by CS-GCNCs in comparison with non-coated GCNCs. The release rate of 5Fu from CS-GCNCs was significantly slower than that of 5Fu from GCNCs, providing sustained release. The release rate could be accelerated by 808-nm laser and microwave co-irradiation. The 5Fu in CS-GCNCs retained high cancer cell killing bioactivity by enhancing the caspase-3 expression level. The cancer cell killing and tumor inhibition efficiencies of the 5Fu-loaded nanomaterials increased significantly under 808-nm laser and microwave co-irradiation. The strong cell killing and tumor ablation activities were due to the synergy of the enhanced GCNC thermal effect caused by laser and microwave co-irradiation and the chemotherapy of 5Fu. Our research opens a door for the development of drug-loaded GCNC-based nano-biomaterials for chemo-photothermal synergistic therapy with the assistance of microwave irradiation.