AI Article Synopsis

  • Understanding how nanoparticles (NPs) are exocytosed from cells helps improve their design for better cellular retention in nanomedicine.
  • Researchers focused on a specific type of gold NP called dodecyl-PEG-AuNP, which has properties that enhance both cellular uptake and exocytosis.
  • The study revealed that these NPs exit cells through an unconventional process, also increasing the secretion of certain small extracellular vesicles, with the mechanism being influenced by the amount of dodecyl on the NP surface.

Article Abstract

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 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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Source
http://dx.doi.org/10.1021/acsnano.1c07418DOI Listing

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