title: Biomimetic glycoliposomes as nanocarriers for targeting P-selectin on activated platelets.
abstract: 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.
authors: Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
authors: Junmin
authors: J
authors: Zhu
authors: Jie
authors: J
authors: Xue
authors: Zhongwu
authors: Z
authors: Guo
authors: Linda
authors: L
authors: Zhang
authors: Roger E
authors: RE
authors: Marchant
mesh_terms: D000818:Animals; D001665:Binding Sites; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D006017:Glycolipids / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007962:Leukocytes / Q000378:metabolism; D007983:Lewis Blood Group Antigens; D008081:Liposomes / Q000138:chemical synthesis / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000097:blood*; D008856:Microscopy, Fluorescence; D053758:Nanoparticles; D009844:Oligosaccharides / Q000737:chemistry; D015539:Platelet Activation; D011092:Polyethylene Glycols / Q000737:chemistry; D014652:Vascular Diseases / Q000097:blood / Q000188:drug therapy
chemical_list: D006017:Glycolipids; D007983:Lewis Blood Group Antigens; D008081:Liposomes; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; C084882:P-selectin ligand protein; C116504:sulfo-Lewis(a); D011092:Polyethylene Glycols