药物递送中的聚合物:载体支持的顺式铂配合物的免疫靶向

Bilha Schechter , Ruth Arnon , Meir Wilchek
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引用次数: 37

摘要

顺铂(CDDP)是一种最有效的抗癌药物,与多羧基载体羧甲基右旋糖酐络合形成铂(II)多重配合物。络合发生在铂配位配合物的氯原子被聚合物侧链上的氢取代,形成载体上相邻羧基的单功能或双功能锚定。该药物与DNA相互作用,对肿瘤细胞具有药理活性。利用单克隆抗体(mAb) 108靶向在KB细胞上过表达的表皮生长因子受体,将该药物载体复合物免疫靶向人表皮样癌(KB)肿瘤。生物素-单克隆抗体与铂(II)-羧甲基右旋糖酐-亲和素缀合物结合,并将免疫复合物注入已建立的皮下KB肿瘤,以评估其在肿瘤内治疗中的作用。结果表明,该免疫复合物具有特异性抑制肿瘤生长的作用。复合物中的抗体必须是肿瘤特异性的,才能将药物载体复合复合物固定在肿瘤部位,因为非生物素化抗体,或用不同特异性的生物素化抗体取代抗kb抗体,会导致抑制作用减弱或消失。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Polymers in drug delivery: immunotargeting of carrier-supported cis-platinum complexes

Cisplatin (CDDP), a most powerful anticancer agent, was complexed to a polycarboxylic carrier carboxymethyldextran to form a platinum(II) multicomplex. Complexing occurs by displacement of the chlorine atoms of the platinum coordination complex by hydrogen of polymer side-chains to form mono- or bifunctional anchoring to adjacent carboxyls on the carrier. The carrier-complexed drug interacted with DNA and was pharmacologically active against tumor cells. The drug-carrier complex was immunotargeted to human epidermoid carcinoma (KB) tumors, using the monoclonal antibody (mAb) 108 directed against the epidermal growth factor receptor that is overexpressed on KB cells. Biotinyl-monoclonal antibody was bound to a platinum(II)-carboxymethyldextran-avidin conjugate and the immune complex was administered into established subcutaneous KB tumors to evaluate its effects upon intratumor treatment. The results showed that the immune complex was specifically effective in inhibiting tumor growth. The antibody in the complex must be tumor-specific to anchor the drug-carrier multicomplex to the tumor site since an unbiotinylated antibody, or replacing the anti-KB antibody by a biotinylated antibody of a different specificity, resulted in reduced or abolished inhibitory effects.

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