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Biocompatible chitosan-carbon nanocage hybrids for sustained drug release and highly efficient laser and microwave co-irradiation induced cancer therapy.

Abstract
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.
AuthorsYuliang Guo, Yang Chen, Pomchol Han, Yuxiong Liu, Wenhao Li, Fangliang Zhu, Kai Fu, Maoquan Chu
JournalActa biomaterialia (Acta Biomater) Vol. 103 Pg. 237-246 (02 2020) ISSN: 1878-7568 [Electronic] England
PMID31843717 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2019. Published by Elsevier Ltd.
Chemical References
  • Biocompatible Materials
  • Delayed-Action Preparations
  • Carbon
  • Chitosan
  • Fluorouracil
Topics
  • Animals
  • Biocompatible Materials (chemistry)
  • Carbon (chemistry)
  • Cell Cycle (drug effects)
  • Cell Death (drug effects)
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • Chitosan (chemistry)
  • Delayed-Action Preparations
  • Drug Liberation
  • Fluorouracil (pharmacology)
  • Lasers
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microwaves
  • Nanoparticles (chemistry, ultrastructure)
  • Neoplasms (therapy)
  • Photothermal Therapy
  • Temperature

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