Targeting of Liposomes via PSGL1 for Enhanced Tumor Accumulation
- Robert CarlisleAffiliated withUniversity of Oxford Email author
- , Leonard W. SeymourAffiliated withUniversity of Oxford
- , Constantin C. CoussiosAffiliated withUniversity of Oxford
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.
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.
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).
The technologies and strategies described here may contribute to clinical improvements in the selectivity and efficacy of liposomal drug delivery agents.
KEY WORDSdrug delivery liposome PSGL1 selectin tumor
- Targeting of Liposomes via PSGL1 for Enhanced Tumor Accumulation
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Volume 30, Issue 2 , pp 352-361
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- drug delivery
- Industry Sectors