Journal
ADVANCED SCIENCE
Volume 7, Issue 4, Pages -Publisher
WILEY
DOI: 10.1002/advs.201902621
Keywords
cell delivery; endocytosis; glycan; immunoglobulin; peptides
Categories
Funding
- National Research, Development and Innovation Office of Hungary [GINOP-2.2.1-15-2016-00007]
- Hungarian Ministry of Innovation and Technology [TUDFO/47138-1/2019-ITM]
- Hungarian National Brain Research Program (MTA-SE-NAP B-BIOMAG)
- Hungarian Academy of Sciences LENDULET-Foldamer
- Finnish TEKES FiDiPro Fellow Grant [40294/13]
- Hungarian Academy of Sciences LENDULET-Biomag
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There is a pressing need to develop ways to deliver therapeutic macromolecules to their intracellular targets. Certain viral and bacterial proteins are readily internalized in functional form through lipid raft-mediated/caveolar endocytosis, but mimicking this process with protein cargoes at therapeutically relevant concentrations is a great challenge. Targeting ganglioside GM1 in the caveolar pits triggers endocytosis. A pentapeptide sequence WYKYW is presented, which specifically captures the glycan moiety of GM1 (K-D = 24 nm). The WYKYW-tag facilitates the GM1-dependent endocytosis of proteins in which the cargo-loaded caveosomes do not fuse with lysosomes. A structurally intact immunoglobulin G complex (580 kDa) is successfully delivered into live HeLa cells at extracellular concentrations ranging from 20 to 160 nm, and escape of the cargo proteins to the cytosol is observed. The short peptidic WYKYW-tag is an advantageous endocytosis routing sequence for lipid raft-mediated/caveolar cell delivery of therapeutic macromolecules, especially for cancer cells that overexpress GM1.
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