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DOI10.1073/pnas.2016974118
Membrane fusion and drug delivery with carbon nanotube porins
Ho N.T.; Siggel M.; Camacho K.V.; Bhaskara R.M.; Hicks J.M.; Yao Y.-C.; Zhang Y.; Köfinger J.; Hummer G.; Noy A.
发表日期2021
ISSN0027-8424
卷号118期号:19
英文摘要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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Carbon nanotube porins; Drug delivery; Liposomes; Membrane fusion
语种英语
scopus关键词carbon nanotube; cholesterol; dimer; dioleoylphosphatidylcholine; doxorubicin; liposome; porin; 108CC15 cell line; animal cell; Article; cancer cell; controlled study; drug delivery system; encapsulation; human; human cell; lipid membrane; lipid vesicle; MDA-MB-231 cell line; membrane fusion; membrane leaflet; molecular dynamics; mouse; nonhuman; priority journal; rat
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/238578
作者单位Materials Science Division, Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94550, United States; School of Natural Sciences, University of California, Merced, CA 93434, United States; Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Frankfurt am Main, 60438, Germany; Department of Regenerative Medicine and Cellular Therapies, University of Nottingham, Nottingham, NG7 2RD, United Kingdom; Institute of Biophysics, Goethe University Frankfurt, Frankfurt am Main, 60438, Germany
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Ho N.T.,Siggel M.,Camacho K.V.,et al. Membrane fusion and drug delivery with carbon nanotube porins[J],2021,118(19).
APA Ho N.T..,Siggel M..,Camacho K.V..,Bhaskara R.M..,Hicks J.M..,...&Noy A..(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).
MLA Ho N.T.,et al."Membrane fusion and drug delivery with carbon nanotube porins".Proceedings of the National Academy of Sciences of the United States of America 118.19(2021).
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