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  Membrane fusion and drug delivery with carbon nanotube porins

Ho, N. T., Siggel, M., Camacho, K. V., Bhaskara, R., Hicks, J. M., Yao, Y.-C., et al. (2021). Membrane fusion and drug delivery with carbon nanotube porins. Proceedings of the National Academy of Sciences of the United States of America, 118(19): e2016974118. doi:10.1073/pnas.2016974118.

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Genre: Journal Article

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 Creators:
Ho, Nga T.1, 2, Author
Siggel, Marc3, Author              
Camacho, Karen V.1, Author
Bhaskara, Ramachandra3, Author              
Hicks, Jacqueline M.1, 4, Author
Yao, Yun-Chiao1, 2, Author
Zhang, Yuliang1, Author
Köfinger, Jürgen3, Author              
Hummer, Gerhard3, 5, Author              
Noy, Aleksandr1, 2, Author
Affiliations:
1Materials Science Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, ou_persistent22              
2School of Natural Sciences, University of California, Merced, CA 93434, ou_persistent22              
3Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society, ou_2068292              
4Department of Regenerative Medicine and Cellular Therapies, University of Nottingham, Nottingham NG7 2RD, United Kingdom, ou_persistent22              
5Institute of Biophysics, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany, ou_persistent22              

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Free keywords: carbon nanotube porins, drug delivery, liposomes, membrane fusion
 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.

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Language(s): eng - English
 Dates: 2020-08-102021-03-262021-05-03
 Publication Status: Published online
 Pages: 8
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1073/pnas.2016974118
BibTex Citekey: ho_membrane_2021
 Degree: -

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Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : PNAS
  Other : Proceedings of the National Academy of Sciences of the USA
  Abbreviation : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
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Affiliations:
Publ. Info: Washington, D.C. : National Academy of Sciences
Pages: - Volume / Issue: 118 (19) Sequence Number: e2016974118 Start / End Page: - Identifier: ISSN: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230