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Biomimetic glycoliposomes as nanocarriers for targeting P-selectin on activated platelets.

Zhu J, Xue J, Guo Z, Zhang L, Marchant RE
Bioconjug Chem. 2007 18 (5): 1366-9

PMID: 17691854 · DOI:10.1021/bc700212b

The cell glycocalyx is an attractive model for surface modification of liposomes with the objectives of tissue targeting and prolonged circulation time. Here, we reported on glycocalyx-mimicking liposomes, prepared by incorporating a glycolipid of 3'-sulfo-Lewis a (SuLe(a))-PEG-DSPE with a headgroup of SuLe(a) and a spacer of poly(ethylene glycol) (PEG) linked to two hydrophobic tails. This PEG spaced structure is used to mimic the extended structure of P-selectin glycoprotein ligand 1 (PSGL-1) on activated leukocytes, in order to facilitate the specific binding of liposomes to the receptor of P-selectin expressed on activated platelets. Our results indicate that SuLe(a)-PEG-DSPE can form stable, narrowly distributed liposomes with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol, with a vesicle size of 113.3 nm. The resultant SuLe(a)-PEG-liposomes can facilitate their binding to the receptor of P-selectin 22 times higher than SuLe(a)-liposomes without a PEG spacer. Further studies by fluorescence microscopy show that SuLe(a)-PEG-liposomes can bind to activated platelets in vitro effectively. It suggests that biomimetic SuLe(a)-PEG-liposomes may be used as nanocarriers to target activated platelets for drug delivery to the injury sites of cardiovascular diseases.

MeSH Terms (17)

Animals Binding Sites Biomimetic Materials Drug Delivery Systems Glycolipids Humans Hydrophobic and Hydrophilic Interactions Leukocytes Lewis Blood Group Antigens Liposomes Membrane Glycoproteins Microscopy, Fluorescence Nanoparticles Oligosaccharides Platelet Activation Polyethylene Glycols Vascular Diseases

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