载有 9-氨基喜树碱的结肠靶向 HPMA 共聚物在荷人结肠癌异种移植瘤小鼠体内的抑瘤作用。
Antitumor efficacy of colon-specific HPMA copolymer/9-aminocamptothecin conjugates in mice bearing human-colon carcinoma xenografts.
机构信息
Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, University of Utah, Salt Lake City, Utah 84112, USA.
出版信息
Macromol Biosci. 2009 Nov 10;9(11):1135-42. doi: 10.1002/mabi.200900147.
Abstract
The antitumor activity of a colon-specific N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer - 9-aminocamptothecin (9-AC) conjugate (P-9-AC) was assessed in orthotopic and subcutaneous animal (HT29 xenograft) tumor models. P-9-AC treatment of mice bearing orthotopic colon tumors, with a dose of 3 mg/kg of 9-AC equivalent every other day for 6 weeks, resulted in regression of tumors in 9 of 10 mice. A lower dose of P-9-AC (1.25 mg/kg of 9-AC equivalent) every other day for 8 weeks inhibited subcutaneous tumor growth in all mice. No liver metastases were observed. Colon-specific release of 9-AC from polymer conjugates enhanced antitumor activity and minimized the systemic toxicity.
摘要
一种结肠特异性 N-(2-羟丙基)甲基丙烯酰胺（HPMA）共聚物-9-氨基喜树碱（9-AC）偶联物（P-9-AC）的抗肿瘤活性在原位和皮下动物（HT29 异种移植）肿瘤模型中进行了评估。用 3 mg/kg 的 9-AC 等效物，每隔一天治疗 6 周，荷有原位结肠肿瘤的小鼠中，9 只中有 10 只肿瘤消退。较低剂量的 P-9-AC（1.25 mg/kg 的 9-AC 等效物），每隔一天治疗 8 周，抑制了所有小鼠的皮下肿瘤生长。未观察到肝转移。聚合物偶联物中 9-AC 的结肠特异性释放增强了抗肿瘤活性，最大限度地减少了全身毒性。
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