1 research outputs found
Intracellular Mechanistic Understanding of 2D MoS<sub>2</sub> Nanosheets for Anti-Exocytosis-Enhanced Synergistic Cancer Therapy
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>i</i>.<i>e</i>., intracellular mechanisms)
remains elusive. Here we chose molybdenum disulfide (MoS<sub>2</sub>) 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. MoS<sub>2</sub> NSs were found to be internalized through three pathways: clathrin
β early endosomes β lysosomes, caveolae β early
endosomes β lysosomes, and macropinocytosis β late endosomes
β lysosomes. We also observed autophagy-mediated accumulation
in the lysosomes and exocytosis-induced efflux of MoS<sub>2</sub> NSs.
Based on these findings, we developed a strategy to achieve effective
and synergistic <i>in vivo</i> cancer therapy with MoS<sub>2</sub> 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