PLGA nanoparticle--peptide conjugate effectively targets intercellular cell-adhesion molecule-1.
Targeted delivery of therapeutics possesses the potential to localize therapeutic agents to a specific tissue as a mechanism to enhance treatment efficacy and abrogate side effects. Antibodies have been used clinically as therapeutic agents and are currently being explored for targeting drug-loaded nanoparticles. Peptides such as RGD peptides are also being developed as an inexpensive and stable alternative to antibodies. In this study, cyclo(1,12)PenITDGEATDSGC (cLABL) peptide was used to target nanoparticles to human umbilical cord vascular endothelial cell (HUVEC) monolayers that have upregulated intercellular cell-adhesion molecule-1 (ICAM-1) expression. The cLABL peptide has been previously demonstrated to possess high avidity for ICAM-1 receptors on the cell surface. Poly( dl-lactic-coglycolic acid) nanoparticles conjugated with polyethylene glycol and cLABL demonstrated rapid binding to HUVEC with upregulated ICAM-1, which was induced by treating cells with the proinflammatory cytokine, interferon-gamma. Binding of the nanoparticles could be efficiently blocked by preincubating cells with free peptide suggesting that the binding of the nanoparticles is specifically mediated by surface peptide binding to ICAM-1 on HUVEC. The targeted nanoparticles were rapidly endocytosed and trafficked to lysosomes to a greater extent than the untargeted PLGA-PEG nanoparticles. Verification of peptide-mediated nanoparticle targeting to ICAM-1 may ultimately lead to targeting therapeutic agents to inflammatory sites expressing upregulated ICAM-1.
Zhang
Na
N
Departments of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, USA.
Chittasupho
Chuda
C
Duangrat
Chadarat
C
Siahaan
Teruna J
TJ
Berkland
Cory
C
D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006016:Glycolates / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D019344:Lactic Acid; D008247:Lysosomes / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013501:Surface-Active Agents / Q000737:chemistry; D015854:Up-Regulation
D004337:Drug Carriers; D006016:Glycolates; D010455:Peptides; D010456:Peptides, Cyclic; D013501:Surface-Active Agents; D018799:Intercellular Adhesion Molecule-1; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols