Design of novel bioconjugates for targeted drug delivery
Design of novel bioconjugates for targeted drug delivery
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DOI：
10.1016/s0168-3659(01)00495-3
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发表时间：
2002-01-17
影响因子：
10.8
通讯作者：
Kopecek, J
中科院分区：
文献类型：
--
作者：
Lu, ZR;Shiah, JG;Kopecek, J
本文总结了基于 N-(2-羟丙基)甲基丙烯酰胺 (HPMA) 共聚物的靶向聚合物生物共轭物的设计和开发的最新工作。已开发出可聚合抗体 Fab' 片段 (MA-Fab')，并用于制备用于治疗人卵巢癌的靶向 HPMA 共聚物-中二氯林 e(6) 缀合物。 MA-Fab'与HPMA共聚的反应性取决于单体双键和抗体Fab'片段之间的间隔基的长度。抗体Fab'片段在掺入HPMA共聚物后保持了生物活性，设计了新型芳香族偶氮间隔基并将其掺入HPMA共聚物-药物（环孢菌素A，9-氨基喜树碱）缀合物中，用于结肠特异性药物递送和结肠疾病的治疗。缀合物的结肠特异性药物释放由药物和间隔物的结构控制。凝集素、麦芽凝集素（WGA）和花生凝集素（PNA）与结肠特异性聚合物药物缀合物缀合，以增强对结肠组织的特异性粘附。 (C) 2002 Elsevier Science B.V. 保留所有权利。
This paper summarizes recent work on the design and development of targeted polymeric bioconjugates based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers. Polymerizable antibody Fab' fragment (MA-Fab') has been developed and used in the preparation of targeted HPMA copolymer-mesochlorin e(6) conjugates for the treatment of human ovarian carcinomas. The reactivity of the MA-Fab' in copolymerization with HPMA depended on the length of the spacer between the monomer double bond and the antibody Fab' fragment. The biological activity of the antibody Fab' fragment was maintained after incorporation into the HPMA copolymer, Novel aromatic azo spacers were designed and incorporated into HPMA copolymer-drug (cyclosporin A, 9-aminocamptothecin) conjugates for the colon-specific drug delivery and for the treatment of colon diseases. The colon-specific drug release from the conjugates was controlled by the structures of both drug and spacers. Lectins, wheat germ agglutinin (WGA) and peanut agglutinin (PNA), were conjugated to the colon-specific polymer drug conjugates to enhance specific adhesion onto colon tissues. (C) 2002 Elsevier Science B.V. All rights reserved.