Biomimetic Glycoliposomes as Nanocarriers for Targeting P-Selectin on Activated Platelets

摘要

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.