Membrane fusion and drug delivery with carbon nanotube porins
Open Access
- 3 May 2021
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 118 (19)
- https://doi.org/10.1073/pnas.2016974118
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.Funding Information
- DOE | SC | Basic Energy Sciences (SCW0972-17)
- DOE | LDRD | Lawrence Livermore National Laboratory (18-ERD-011)
- National Science Foundation (1710211)
- RCUK | Engineering and Physical Sciences Research Council (EP/R004072/1)
- LOEWE (DynaMem)
This publication has 44 references indexed in Scilit:
- Advances in Drug DeliveryAnnual Review of Materials Research, 2011
- Electron transfer from Proteus vulgaris to a covalently assembled, single walled carbon nanotube electrode functionalised with osmium bipyridine complex: Application to a whole cell biosensorBiosensors and Bioelectronics, 2011
- pH-Tunable Ion Selectivity in Carbon Nanotube PoresLangmuir, 2010
- Paradoxical glomerular filtration of carbon nanotubesProceedings of the National Academy of Sciences of the United States of America, 2010
- [186Re]Liposomal doxorubicin (Doxil): in vitro stability, pharmacokinetics, imaging and biodistribution in a head and neck squamous cell carcinoma xenograft modelNuclear Medicine and Biology, 2009
- Viral membrane fusionNature Structural & Molecular Biology, 2008
- Canonical sampling through velocity rescalingThe Journal of Chemical Physics, 2007
- Virus membrane-fusion proteins: more than one way to make a hairpinNature Reviews Microbiology, 2006
- Chemotherapy and the war on cancerNature Reviews Cancer, 2005
- Use of resonance energy transfer to monitor membrane fusionBiochemistry, 1981