PEG-PE/phosphatidylcholine mixed immunomicelles specifically deliver encapsulated taxol to tumor cells of different origin and promote their efficient killing.
Mixed micelles were prepared from poly(ethyleneglycol)-distearyl phosphoethanolamine (PEG2000-PE) and egg phosphatidylcholine. The micelles were covalently modified with the nucleosome-specific monoclonal antibody 2C5 known to recognize and bind a variety of tumor cells via their surface-bound nucleosomes. Covalent attachment of 2C5 antibody was performed via a micelle-incorporated PEG-PE with the distal terminus of the PEG block activated with p-nitrophenylcarbonyl group (pNP-PEG-PE). Micelle surface-attached 2C5 antibody maintained its specific activity. 2C5-targeted immunomicelles were able to carry more than 3 wt% of taxol. Taxol-loaded immunomicelles specifically recognized tumor cell lines of several types. The cytotoxicity of 2C5-targeted taxol-loaded immunomicelles in a cell culture model was much higher when compared with free taxol or taxol in non-targeted micelles.
Gao
Z
Z
Department of Pharmaceutical Sciences, Bouve College of Health Sciences, Northeastern Univeristy, Boston, MA 02115, USA.
Lukyanov
A N
AN
Chakilam
A R
AR
Torchilin
V P
VP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D004591:Electrophoresis, Polyacrylamide Gel; D051379:Mice; D008823:Micelles; D009707:Nucleosomes / Q000276:immunology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D009707:Nucleosomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D017239:Paclitaxel