Dendrimer-platinate: a novel approach to cancer chemotherapy
Dendrimer-platinate: a novel approach to cancer chemotherapy
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DOI：
10.1097/00001813-199909000-00010
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发表时间：
1999-09-01
影响因子：
2.3
通讯作者：
Duncan, R
中科院分区：
文献类型：
--
作者：
Malik, N;Evagorou, EG;Duncan, R
将具有羧酸钠表面的聚酰胺-胺（PAMAM（R））树状聚合物3.5代与顺铂缀合，得到树状聚合物-铂酸盐（树状聚合物-Pt; 20-25重量%铂），其是高度水溶性的并且在体外缓慢释放铂。在体内，树枝状聚合物-Pt和顺铂腹膜内对腹膜内L1210具有同等活性，并且在腹膜内给予的高剂量树枝状聚合物-Pt显示出对腹膜内B16 F10的活性，而顺铂没有。此外，当静脉内给药治疗可触及的s.c. B16 F10黑色素瘤，树枝状聚合物-Pt显示出抗肿瘤活性，而顺铂是无活性的，静脉注射顺铂（1 mg/kg）或树枝状聚合物-Pt后血液和组织中铂水平的测量（15 mg/kg）-这些化合物的最大耐受剂量（MTD）-通过EPR效应显示树枝状聚合物-Pt在实体瘤组织中的选择性积累（与顺铂相比，曲线下面积增加50倍）。树枝状聚合物-Pt的毒性也比顺铂低（3至15倍），因此具有作为新的抗肿瘤方法进行进一步研究的潜力。[(C)1999 Lippincott威廉姆斯& Wilkins]。
A polyamidoamine (PAMAM(R)) dendrimer generation 3.5 with a sodium carboxylate surface was conjugated to cisplatin giving a dendrimer-platinate (dendrimer-Pt; 20-25 wt% platinum) which was highly water soluble and released platinum slowly in vitro. In vivo the dendrimer-Pt and cisplatin were equi-active i.p. against i.p. L1210, and at high dose dendrimer-Pt given i.p. showed activity against i.p. B16F10 whereas cisplatin did not. Additionally, when administered i.v. to treat a palpable s.c. B16F10 melanoma, the dendrimer-Pt displayed antitumor activity whereas cisplatin was inactive, Measurement of platinum levels in blood and tissues after i.v. injection of cisplatin (1 mg/kg) or dendrimer-Pt (15 mg/kg)-the maximum tolerated dose (MTD) of these compounds-showed selective accumulation of the dendrimer-Pt in solid tumor tissue by the EPR effect (a 50-fold increase in area under curve compared with cisplatin), The dendrimer-Pt was also less toxic (3- to 15-fold) than cisplatin and thus has potential for further investigation as a novel antitumor approach. [(C) 1999 Lippincott Williams & Wilkins].