The use of tail-anchored protein chimeras to enhance liposomal cargo delivery

PloS One
Abbi AbdelrehimLynda K Harris

Abstract

Liposomes are employed as drug delivery vehicles offering a beneficial pharmacokinetic/distribution mechanism for in vivo therapeutics. Therapeutic liposomes can be designed to target specific cell types through the display of epitope-specific targeting peptides on their surface. The majority of peptides are currently attached by chemical modification of lipid constituents. Here we investigate an alternative and novel method of decorating liposomes with targeting ligand, using remotely and spontaneously inserting chimeric tail-anchored membrane (TA) proteins to drug loaded liposomes. An artificial TA protein chimera containing the transmembrane domain from the spontaneously inserting TA protein cytochrome b5 (Cytb5) provided a robust membrane tether for the incorporation of three different targeting moieties into preformed liposomes. The moieties investigated were the transactivator of transcription (TAT) peptide, the EGF-receptor binding sequence GE11 and the placental and tumour homing ligand CCGKRK. In all cases, TA protein insertion neither significantly altered the size of the liposomes nor reduced drug loading. The efficacy of this novel targeted delivery system was investigated using two human cell lines, HeLa M and BeWo...Continue Reading

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Methods Mentioned

BETA
size exclusion chromatography
dynamic light scattering
transmission electron microscopy
flow cytometry
dynamic
electron microscopy

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