4.8 Article

Mammalian Cells Exocytose Alkylated Gold Nanoparticles via Extracellular Vesicles

期刊

ACS NANO
卷 16, 期 2, 页码 2032-2045

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acsnano.1c07418

关键词

alkylation; exocytosis; gold nanoparticles; extracellular vesicles; exosomes; multivesicular bodies; lysosomes

资金

  1. Chow Yuk Ho Technology Centre for Innovative Medicine
  2. Chinese University of Hong Kong (CUHK)
  3. General Research Fund (GRF) from the Research Grants Council (RGC) [14300718]
  4. Croucher Innovation Award from the Croucher Foundation

向作者/读者索取更多资源

Understanding the mechanism of nanoparticle exocytosis from cells is important for designing nanoparticles with desirable cellular retention for nanomedicine applications. This study investigates the exocytosis mechanism of dodecyl-terminated, polyethylene glycol-coated gold nanoparticles and finds that the presence of alkyl chains promotes cellular uptake and improves exocytosis efficiency.
Understanding the exocytosis of nanoparticles (NPs) from cells is valuable because it informs design rules of NPs that support desirable cellular retention for nanomedicine applications, but investigations into the mechanism for the exocytosis of NPs remain scarce. We elucidate the mechanism for the exocytosis of dodecyl-terminated, polyethylene glycol-coated gold NPs (termed dodecyl-PEG-AuNP). The Au core enables ultrastructural differentiation of the exocytosed NPs from the nearby extracellular vesicles (EVs). The PEG shell prevents interparticle agglomeration or aggregation that disfavors exocytosis. The minute amounts of alkyl chains on the PEG shell not only promote cellular uptake but also improve exocytosis by up to 4-fold higher probability and upregulate exocytosis- and vesicle-related genes. After entering Kera-308 keratinocytes and trafficking to multivesicular bodies and lysosomes, these NPs exit the cell predominantly via unconventional exocytosis, accompanied by enhanced secretion of sub-100 nm, CD81-enriched exosomes. The pathway for NP exocytosis and subpopulation of EVs that are secreted alongside the exocytosed NPs depends on dodecyl loading. This work provides insights into dissecting the mechanism of NP exocytosis and its relationship with EV secretion.

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