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- Title
Targeting of Liposomes via PSGL1 for Enhanced Tumor Accumulation.
- Authors
Carlisle, Robert; Seymour, Leonard; Coussios, Constantin
- Abstract
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.
- Subjects
TUMOR treatment; LIPOSOMES; TARGETED drug delivery; DRUG delivery systems; P-selectin glycoprotein ligand-1; ENDOTHELIUM; PHARMACOKINETICS
- Publication
Pharmaceutical Research, 2013, Vol 30, Issue 2, p352
- ISSN
0724-8741
- Publication type
Article
- DOI
10.1007/s11095-012-0875-5