Antitumor Efficacy of Colon-Specific HPMA Copolymer/9-Aminocamptothecin Conjugates in Mice Bearing Human-Colon Carcinoma Xenografts
Antitumor Efficacy of Colon-Specific HPMA Copolymer/9-Aminocamptothecin Conjugates in Mice Bearing Human-Colon Carcinoma Xenografts
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DOI：
10.1002/mabi.200900147
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发表时间：
2009-11-10
影响因子：
4.6
通讯作者：
Kopecek, Jindrich
中科院分区：
文献类型：
--
作者：
Gao, Song-Qi;Sun, Yongen;Kopecek, Jindrich
在原位和皮下动物（HT 29异种移植物）肿瘤模型中评估结肠特异性N-（2-羟丙基）甲基丙烯酰胺（HPMA）共聚物-9-氨基喜树碱（9-AC）缀合物（P-9-AC）的抗肿瘤活性。对携带原位结肠肿瘤的小鼠进行P-9-AC治疗，每隔一天给予3 mg/kg 9-AC当量，持续6周，导致10只小鼠中有9只的肿瘤消退。较低剂量的P-9-AC（1.25 mg/kg 9-AC当量）每隔一天给药一次，持续8周，可抑制所有小鼠的皮下肿瘤生长。未观察到肝转移。从聚合物缀合物中结肠特异性释放9-AC增强了抗肿瘤活性并最小化了全身毒性。
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.