Gao Z, Lukyanov A N, Chakilam A R, Torchilin V P
Department of Pharmaceutical Sciences, Bouve College of Health Sciences, Northeastern Univeristy, Boston, MA 02115, USA.
J Drug Target. 2003 Feb;11(2):87-92. doi: 10.1080/1061186031000138623.
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.
混合胶束由聚乙二醇-二硬脂酰磷脂酰乙醇胺(PEG2000-PE)和鸡蛋卵磷脂制备而成。这些胶束用核小体特异性单克隆抗体2C5进行共价修饰,已知该抗体可通过其表面结合的核小体识别并结合多种肿瘤细胞。2C5抗体的共价连接是通过胶束掺入的PEG-PE进行的,其中PEG嵌段的远端用对硝基苯基羰基(pNP-PEG-PE)活化。胶束表面连接的2C5抗体保持其特异性活性。靶向2C5的免疫胶束能够携带超过3 wt%的紫杉醇。负载紫杉醇的免疫胶束特异性识别多种类型的肿瘤细胞系。与游离紫杉醇或非靶向胶束中的紫杉醇相比,在细胞培养模型中,靶向2C5的负载紫杉醇的免疫胶束的细胞毒性要高得多。