Abstract
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).
Highlights
Two-dimensional (2D) materials, such as transition-metal dichalcogenide nanosheets (TMD NSs), black phosphorus NSs, MXene, and so on, have shown promising achievements in various biomedical applications including cancer photothermal therapy (PTT) [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]
The prepared WS2 NSs were coated by lipoic acid (LA)-PEG to improve their dispersability, stability, and biocompatibility
Based on our previous studies on the intracellular fate of 2D MoS2 NSs in cancer cells and their application in drug delivery platform-based anti-exocytosis-enhanced cancer treatment [27], we here aimed to reveal the detailed pathways of 2D WS2 NS-based photothermal agents (PTAs) within the cancer cells, explore the influence of the composition difference on NSs’ intracellular fate, and confirm whether the exocytosis inhibition strategy could be a universal one for other therapeutic modalities such as single PTAs to achieve combination cancer therapy
Summary
Two-dimensional (2D) materials, such as transition-metal dichalcogenide nanosheets (TMD NSs), black phosphorus NSs, MXene, and so on, have shown promising achievements in various biomedical applications including cancer photothermal therapy (PTT) [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]. The intracellular fate of the nanomaterials (e.g. internalization, intracellular trafficking, and excretion) is one of the most important nano-bio interactions that is closely related to their safety issues [25,26,27]. As these activities occur toward the end period of their journey in the biosystem, they are usually crucial factors in determining the final therapeutic effects of various modalities of 2D material-based. Systematic experimental studies of the intracellular fate of the 2D NSs still remain rare and largely unexplored up to now [21, 24, 25]
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