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Membrane fusion and drug delivery with carbon nanotube porins

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Siggel,  Marc
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society;

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Bhaskara,  Ramachandra
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society;

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Köfinger,  Jürgen
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society;

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Hummer,  Gerhard
Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society;
Institute of Biophysics, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany;

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Citation

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.


Cite as: http://hdl.handle.net/21.11116/0000-0008-7AAF-B
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.