Biomimetic glycoliposomes as nanocarriers for targeting P-selectin on activated platelets.
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.
Zhu
Junmin
J
Department of Biomedical Engineering, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
Xue
Jie
J
Guo
Zhongwu
Z
Zhang
Linda
L
Marchant
Roger E
RE
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
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