Comprehensive insights into intracellular fate of WS2 nanosheets for enhanced photothermal therapeutic outcomes via exocytosis inhibition

Abstract

Two-dimensional (2D) nanosheet (NS)-based photothermal agents (PTAs), such as transition-metal dichalcogenides, have shown immense potential for their use in cancer photothermal therapy (PTT). However, the nano-bio interaction study regarding these NS-based PTAs is still in its infancy. In this study, we used WS2-PEG NS-based PTA as an example to provide comprehensive insights into the experimental understanding of their fate in cancer cells. The data revealed that three different endocytosis pathways (macropinocytosis, clathrin-dependent, and caveolae-dependent endocytosis), autophagy-mediated lysosome accumulation, and exocytosis-induced excretion contribute to the integrated pathways of WS2-PEG NSs within cells. These pathways are consistent with our previous reports on MoS2-PEG NS-based drug delivery platform, indicating that the composition difference of 2D NSs with PEGylation may have little influence on their intercellular fate. Moreover, by blocking the revealed exocytosis pathway-mediated secretion of WS2 NSs in tumor cells, an effective approach is proposed to attain enhanced photothermal therapeutic outcomes with low doses of WS2 NSs and under a low power of a near-infrared (NIR) laser. We expect that the exocytosis inhibition strategy may be a universal one for 2D NSs to achieve combination cancer therapy. This study may also provide more experimental basis for the future development of 2D NS’s application in biomedicine (e.g. PTT).

Keywords

• ws2 nanosheets
• photothermal agents
• intracellular fate
• exocytosis inhibition
• enhanced photothermal therapy