Cyanine lipids promote the shedding of extracellular vesicles from cell membranes

Hanmant Gaikwad, David Siegel, Ashlynn Barnes, Masamitsu Kanada, Chun Wan, Jingshi Shen, Irina V. Balyasnikova, Dmitri Simberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Extracellular vesicles (EV) have garnered significant attention in drug delivery, imaging, and immu-notherapy. There is a need for methods to enhance the release of EV from cells. We found that at high labeling concentrations (100µM), indocarbocyanine lipids DiD and DiR that are commonly used for labeling cells, nanoparticles, and EV, promoting the shedding of cell membrane tetraspanins with con-comitant release of EV in the medium. We screened a library of lipids and liposomal formulations to investigate this phenomenon further to release membrane marker CD63 from THP-1 cells and membrane red-enhanced nanolantern (RNL) from 4T1 cells. We found a strong dependency of the EV release on lipid structure. In general, lipids that had a cyanine headgroup were more efficient than PEGylated phospholipids, neutral and cationic liposomes, with some lipids enhancing the release of CD63 up to 4-fold and of RNL up to 8-fold, over vehicle-treated control. A side-by-side comparison of cyanine lipid derivatives and corresponding precursor lipids confirmed that the cyanine headgroup sig-nificantly promoted the shedding of RNL. Mutation of an exosome biogenesis regulator UNC13D did not hinder the release. Lipid-released EV could be modified with anti-interleukin 13 receptor alpha 2 antibody and targeted to glioma cells, suggesting potential utility in drug delivery. Furthermore, the impact of extraneously added lipids should be carefully considered in cell labeling and drug delivery applications.

Original languageEnglish (US)
Pages (from-to)1066-1077
Number of pages12
JournalPrecision Nanomedicine
Volume6
Issue number3
DOIs
StatePublished - 2023

Funding

The study was supported by the NIH grant R01CA194058 to DS and IVB and AB Nexus grant from the University of Colorado to DS and GS. The study was supported by the NIH grant R01CA194058 to DS and IVB and AB Nexus grant from the nUiversity foo loCrado to SDnad SG.

Keywords

  • antibody
  • cells
  • delivery
  • exosomes
  • extracellular vesicles
  • lipids
  • targeting

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, medical
  • Pharmaceutical Science

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