Membrane fusion and drug delivery with carbon nanotube porins

Nga T. Ho, Marc Siggel, Karen V. Camacho, Ramachandra M. Bhaskara, Jacqueline M. Hicks, Yun Chiao Yao, Yuliang Zhang, Jürgen Köfinger, Gerhard Hummer, Aleksandr Noy

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Drug delivery mitigates toxic side effects and poor pharmacokinetics of life-saving therapeutics and enhances treatment efficacy. However, direct cytoplasmic delivery of drugs and vaccines into cells has remained out of reach. We find that liposomes studded with 0.8-nm-wide carbon nanotube porins (CNTPs) function as efficient vehicles for direct cytoplasmic drug delivery by facilitating fusion of lipid membranes and complete mixing of the membrane material and vesicle interior content. Fusion kinetics data and coarse-grained molecular dynamics simulations reveal an unusual mechanism where CNTP dimers tether the vesicles, pull the membranes into proximity, and then fuse their outer and inner leaflets. Liposomes containing CNTPs in their membranes and loaded with an anticancer drug, doxorubicin, were effective in delivering the drug to cancer cells, killing up to 90% of them. Our results open an avenue for designing efficient drug delivery carriers compatible with a wide range of therapeutics.

Original languageEnglish (US)
Article numbere2016974118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number19
DOIs
StatePublished - May 11 2021
Externally publishedYes

Keywords

  • Carbon nanotube porins
  • Drug delivery
  • Liposomes
  • Membrane fusion

ASJC Scopus subject areas

  • General

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