Pinocytosis

Cell biology

Nanoparticle

Biology

Materials science

Lysosome

Apoptosis

Autophagy

Signal transduction

Biochemistry

Secretion

Nanotoxicology

Endocytosis

Exocytosis

Intracellular

Genetics

Endosome

Nanotechnology

Nanomedicine

Enzyme

Nanomaterials

Chemistry

Cell

Caveolae

Cancer

Cancer cell

ACS Nano

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.

Intracellular Mechanistic Understanding of 2D MoS<sub>2</sub> Nanosheets for Anti-Exocytosis-Enhanced Synergistic Cancer Therapy

Intracellular Mechanistic Understanding of 2D MoS2 Nanosheets for Anti-Exocytosis-Enhanced Synergistic Cancer Therapy

Intracellular Mechanistic Understanding of 2D MoS₂ Nanosheets for Anti-Exocytosis-Enhanced Synergistic Cancer Therapy