Molecular vehicles for targeted drug delivery.
Targeted drug delivery by cell-specific cytokines and antibodies promises greater drug efficacy and reduced side effects. We describe a novel strategy for assembly of drug delivery vehicles that does not require chemical modification of targeting proteins. The strategy relies on a noncovalent binding of standardized "payload" modules to targeting proteins expressed with a "docking" tag. The payload modules are constructed by linking drug carriers to an adapter protein capable of binding to a docking tag. Using fragments of bovine ribonuclease A as an adapter protein and a docking tag, we have constructed vascular endothelial growth factor (VEGF) based vehicles for gene delivery and for liposome delivery. Assembled vehicles displayed remarkable selectivity in drug delivery to cells overexpressing VEGF receptors. We expect that our strategy can be employed for targeted delivery of many therapeutic or imaging agents by different recombinant targeting proteins.
Backer
Marina V
MV
SibTech, Inc., Newington, Connecticut 06111, USA. mbacker@sibtech.com
Aloise
Renee
R
Przekop
Kristen
K
Stoletov
Konstantin
K
Backer
Joseph M
JM
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D016503:Drug Delivery Systems; D016228:Endothelial Growth Factors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015316:Genetic Therapy; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008081:Liposomes; D008222:Lymphokines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000378:metabolism; D010957:Plasmids; D011094:Polyethyleneimine / Q000737:chemistry / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D012260:Ribonucleases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008081:Liposomes; D008222:Lymphokines; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C023560:ribonuclease S-peptide; D011094:Polyethyleneimine; D040262:Receptors, Vascular Endothelial Growth Factor; D012260:Ribonucleases