Polymeric particles conjugated with a ligand to VCAM-1 exhibit selective, avid, and focal adhesion to sites of atherosclerosis.
The increased expression of VCAM-1 on endothelial segments within plaque regions could be used as a target to deliver polymeric drug carriers selectively to sites of atherosclerosis. We probed the hypothesis that polymeric particles conjugated with a ligand for VCAM-1 exhibit selective and avid adhesion to sites of atherosclerosis. Particles made from polystyrene or the biodegradable polymer poly(sebacic acid)-block-polyethylene glycol (PSA-PEG) were conjugated with an antibody to VCAM-1 (alpha-VCAM-1) or IgG (negative control). The particles were injected into the jugular vein of ApoE(-/-) (a murine model of atherosclerosis) or wild type mice and their adhesion to the aorta determined. alpha-VCAM-1 particles exhibited significantly greater adhesion to ApoE(-/-) mouse aorta [32 +/- 5 (mean +/- SEM) particles/mm(2) for polystyrene particles and 31 +/- 7 particles/mm(2) for PSA-PEG particles] compared to the level of adhesion to wild type mouse aorta (18 +/- 1 particles/mm(2) for polystyrene particles and 6 +/- 1 particles/mm(2) for PSA-PEG particles). Within ApoE(-/-) mice, the alpha-VCAM-1 particles exhibited significantly greater adhesion to the aorta (32 +/- 5 particles/mm(2) for polystyrene particles and 31 +/- 7 particles/mm(2) for PSA-PEG particles) compared to the adhesion of IgG particles (1 +/- 1 particles/mm(2) for polystyrene particles and 2 +/- 1 particles/mm(2) for PSA-PEG particles). Detailed analysis of the adhesion revealed that alpha-VCAM-1 particles exhibited focal adhesion to plaque regions, in particular the periphery of the plaques, within the ApoE(-/-) mouse aorta. Combined the data demonstrate that polymeric particles conjugated with a ligand to VCAM-1 exhibit selective, avid and focal adhesion to sites of atherosclerosis providing strong evidence that VCAM-1 ligand bearing polymeric particles could be used for targeting drugs selectively to atherosclerotic tissue.
Deosarkar
Sudhir P
SP
Department of Chemical and Biomolecular Engineering, Ohio University, Athens, Ohio 45701, USA.
Malgor
Ramiro
R
Fu
Jie
J
Kohn
Leonard D
LD
Hanes
Justin
J
Goetz
Douglas J
DJ
D000704:Analysis of Variance; D000812:Anhydrides / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001011:Aorta / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism*; D004337:Drug Carriers / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D011092:Polyethylene Glycols / Q000378:metabolism*; D011137:Polystyrenes / Q000378:metabolism*; D013379:Substrate Specificity; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D000812:Anhydrides; D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D008024:Ligands; D011137:Polystyrenes; D019010:Vascular Cell Adhesion Molecule-1; C405032:poly(sebacic anhydride)-b-polyethylene glycol; D011092:Polyethylene Glycols