Institute of Macromolecular Chemistry , Czech Academy of Sciences , Heyrovského nám. 2 , 162 06 Prague 6 , Czech Republic.
Institute of Molecular Genetics , Czech Academy of Sciences , Flemingovo nám. 2 , 166 10 Prague 6 , Czech Republic.
Biomacromolecules. 2019 Jan 14;20(1):412-421. doi: 10.1021/acs.biomac.8b01616. Epub 2018 Dec 7.
A water-soluble polymer cancerostatic actively targeted against cancer cells expressing a disialoganglioside antigen GD2 was designed, synthesized and characterized. A polymer conjugate of an antitumor drug doxorubicin with a N-(2-hydroxypropyl)methacrylamide-based copolymer was specifically targeted against GD2 antigen-positive tumor cells using a recombinant single chain fragment (scFv) of an anti-GD2 monoclonal antibody. The targeting protein ligand was attached to the polymer-drug conjugate either via a covalent bond between the amino groups of the protein using a traditional nonspecific aminolytic reaction with a reactive polymer precursor or via a noncovalent but highly specific interaction between bungarotoxin covalently linked to the polymer and the recombinant scFv modified with a C-terminal bungarotoxin-binding peptide. The GD2 antigen binding activity and GD2-specific cytotoxicity of the targeted noncovalent polymer-scFv complex proved to be superior to the covalent polymer-scFv conjugate.
设计、合成并表征了一种针对表达二唾液酸神经节苷脂抗原 GD2 的癌细胞的水溶性聚合物抗癌剂。使用抗 GD2 单克隆抗体的重组单链片段 (scFv)，将抗肿瘤药物阿霉素与基于 N-(2-羟丙基)甲基丙烯酰胺的共聚物的聚合物缀合物特异性靶向 GD2 抗原阳性肿瘤细胞。靶向蛋白配体通过使用反应性聚合物前体的传统非特异性氨裂解反应在蛋白质的氨基之间形成共价键，或者通过共价连接到聚合物上的邦戈毒素与用 C 末端邦戈毒素结合肽修饰的重组 scFv 之间的非共价但高度特异性相互作用连接到聚合物-药物缀合物上。靶向非共价聚合物-scFv 复合物的 GD2 抗原结合活性和 GD2 特异性细胞毒性被证明优于共价聚合物-scFv 缀合物。
