期刊
ACS NANO
卷 12, 期 3, 页码 2922-2938出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b00516
关键词
two-dimensional nanosheets; MoS2; intracellular trafficking network; nano-bio interactions; enhanced cancer therapy
类别
资金
- US National Institutes of Health (NIH) [HL127464]
- David H. Koch-Prostate Cancer Foundation (PCF) Program in Cancer Nanotherapeutics
- National Research Foundation of Korea [K1A1A2048701]
- Natural Science Foundation of Guangdong Province [2016A030310023]
- China Postdoctoral Science Foundation [2016M600676]
- Tsinghua Scholarship for Overseas Graduate Studies [2013159]
Emerging two-dimensional (2D) nanomaterials, such as transition-metal dichalcogenide (TMD) nanosheets (NSs), have shown tremendous potential for use in a wide variety of fields including cancer nanomedicine. The interaction of nanomaterials with biosystems is of critical importance for their safe and efficient application. However, a cellular-level understanding of the nano-bio interactions of these emerging 2D nanomaterials (i.e., intracellular mechanisms) remains elusive. Here we chose molybdenum disulfide (MoS2) NSs as representative 2D nanomaterials to gain a better understanding of their intracellular mechanisms of action in cancer cells, which play a significant role in both their fate and efficacy. MoS2 NSs were found to be internalized through three pathways: clathrin -> early endosomes -> lysosomes, caveolae -> early endosomes -> lysosomes, and macropinocytosis -> late endosomes -> lysosomes. We also observed autophagy-mediated accumulation in the lysosomes and exocytosis-induced efflux of MoS2 NSs. Based on these findings, we developed a strategy to achieve effective and synergistic in vivo cancer therapy with MoS2 NSs loaded with low doses of drug through inhibiting exocytosis pathway-induced loss. To the best of our knowledge, this is the first systematic experimental report on the nano-bio interaction of 2D nanomaterials in cells and their application for anti-exocytosis-enhanced synergistic cancer therapy.
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