Targeting of liposomes via PSGL1 for enhanced tumor accumulation

Journal article

Purpose: 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. © 2012 The Author(s).

Authors: Carlisle, R; Seymour, L; Coussios, C

• Journal: Pharmaceutical Research
• Volume: 30
• Issue: 2
• Pages: 352-361
• Publication date: 2013-02-01
• DOI: 10.1007/s11095-012-0875-5
• EISSN: 1573-904X
• ISSN: 0724-8741
• Language: English
• Keywords: tumor; liposome; drug delivery; PSGL1; selectin