title: Targeting of liposomes via PSGL1 for enhanced tumor accumulation.
abstract: OBJECTIVE
  To improve the delivery of liposomes to tumors using P-selectin glycoprotein ligand 1 (PSGL1) mediated binding to selectin molecules, which are upregulated on tumorassociated endothelium.
  
  
  METHODS
  PSGL1 was orientated and presented on the surface of liposomes to achieve optimal selectin binding using a novel streptavidin-protein G linker molecule. Loading of PSGL1 liposomes with luciferin allowed their binding to e-selectin and activated HUVEC to be quantified in vitro and their stability, pharmacokinetics and tumor accumulation to be tested in vivo using murine models.
  
  
  RESULTS
  PSGL1 liposomes showed 5-fold (p < 0.05) greater selectin binding than identically formulated control liposomes modified with ligand that did not contain the selectin binding domain. When added to HUVEC, PSGL1 liposomes showed >7-fold (p < 0.001) greater attachment than control liposomes. In in vivo studies PSGL1 liposomes showed similar stability and circulation to control liposomes but demonstrated a >3-fold enhancement in the level of delivery to tumors (p < 0.05).
  
  
  CONCLUSIONS
  The technologies and strategies described here may contribute to clinical improvements in the selectivity and efficacy of liposomal drug delivery agents.
authors.affiliation: University of Oxford, Oxford, UK. robert.carlisle@oncology.ox.ac.uk
authors.forename: Robert
authors.initials: R
authors.lastname: Carlisle
authors.forename: Leonard W
authors.initials: LW
authors.lastname: Seymour
authors.forename: Constantin C
authors.initials: CC
authors.lastname: Coussios
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D019007:P-Selectin / Q000276:immunology; D013499:Surface Properties
chemical_list: D052160:Benzothiazoles; C532924:D-luciferin; D008081:Liposomes; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein