Comparison of the uptake mechanisms of zwitterionic and negatively charged liposomes by HeLa cells

Daphne Montizaan, Keni Yang, Catharina Reker-Smit, Anna Salvati*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)
37 Downloads (Pure)


Zwitterionic molecules are used as an alternative to PEGylation to reduce protein adsorption on nanocarriers. Nonetheless, little is known on the effect of zwitterionic modifications on the mechanisms cells use for nanocarrier uptake. In this study, the uptake mechanism of liposomes containing zwitterionic or negatively charged lipids was characterized using pharmacological inhibitors and RNA interference on HeLa cells to block endocytosis. As expected, introducing zwitterionic lipids reduced protein adsorption in serum, as well as uptake efficiency. Blocking clathrin-mediated endocytosis strongly decreased the uptake of the negatively charged liposomes, but not the zwitterionic ones. Additionally, inhibition of macropinocytosis reduced uptake of both liposomes, but blocking actin polymerization had effects only on the negatively charged ones. Overall, the results clearly indicated that the two liposomes were internalized by HeLa cells using different pathways. Thus, introducing zwitterionic lipids affects not only protein adsorption and uptake efficiency, but also the mechanisms of liposome uptake by cells.
Original languageEnglish
Article number102300
Number of pages10
JournalNanomedicine-Nanotechnology biology and medicine
Publication statusPublished - Nov-2020

Cite this