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. STATEMENT OF SIGNIFICANCE: Graphitic
carbon nanocages (GCNCs) are
graphene-based nanomaterials that can be used for both drug loading and
cancer photothermal therapy (PTT). Herein, we showed that
chitosan (CS)-GCNCs hybrid
biomaterials had very low cytotoxicity, high ability for loading drug, and exhibited sustained drug release. In particular, although low-power microwaves alone are unable to trigger
cancer cell damage by GCNCs, the cell killing and mouse
tumor inhibition efficiencies were significantly improved by near-infrared (NIR)
laser and microwave co-irradiation compared with
laser-triggered PTT alone. This combined use of
laser and microwave co-irradiation promises essential therapeutic modality and opens a new avenue for PTT.