Synthesis and antitumor activity of doxorubicin conjugated stearic acid-g-chitosan oligosaccharide polymeric micelles
Synthesis and antitumor activity of doxorubicin conjugated stearic acid-g-chitosan oligosaccharide polymeric micelles
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DOI：
10.1016/j.biomaterials.2009.09.008
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发表时间：
2009-12-01
期刊：
影响因子：
14
通讯作者：
Yuan, Hong
中科院分区：
文献类型：
--
作者：
Hu, Fu-Qiang;Liu, Li-Na;Yuan, Hong
本文通过抗癌药物阿霉素（DOX）与硬脂酸接枝壳寡糖（CSO-SA）之间的顺乌头基键合成了阿霉素缀合硬脂酸-g-壳寡糖聚合胶束（DOX-CSO-SA）。 CSO-SA 胶束已被证明具有更快的肿瘤细胞内化能力。这里，使用氨基取代度(SD%)为6.47%的CSO-SA来合成DOX-CSO-SA。临界胶束浓度(CMC)约为0.14 mg mL(-1)。 CSO-SA浓度为1 mg·mL(-1)的胶束数均直径为32.7 nm,粒径分布较窄,表面电位为51.5 mV。 DOX-CSO-SA与阿霉素结合后，CMC下降；胶束尺寸增大；且zeta电位下降。 DOX-CSO-SA 胶束表现出 pH 依赖性 DOX 释放行为。随着释放介质的pH值从7.2降低到5.0，DOX从DOX-CSO-SA胶束中的释放速率显着增加。 DOX-CSO-SA胶束对人乳腺癌（MCF-7）细胞及其多重耐药（MCF-7/Adr）细胞的体外抗肿瘤活性测试显示出对DOX耐药MCF-7细胞（MCF-7/Adr）的逆转活性。体内抗肿瘤活性结果表明，与市售盐酸阿霉素注射液相比，DOX-CSO-SA胶束治疗能有效抑制肿瘤生长，并降低对动物体的毒性。 (C) 2009 Elsevier Ltd. 保留所有权利。
Doxorubicin conjugated stearic acid-g-chitosan oligosaccharide polymeric micelles (DOX-CSO-SA) was synthesized via cis-aconityl bond between the anticancer drug doxorubicin (DOX) and stearic acid grafted chitosan oligosaccharide (CSO-SA) in this paper. The CSO-SA micelles had been demonstrated faster internalization ability into tumor cells. Here, the CSO-SA with 6.47% amino substituted degree (SD%) was used to synthesize DOX-CSO-SA. The critical micelle concentration (CMC) was about 0.14 mg mL(-1). The micelles with 1 mg mL(-1) CSO-SA concentration had 32.7 nm number average diameter with a narrow size distribution and 51.5 mV surface potential. After conjugating with doxorubicin, CMC of DOX-CSO-SA descended; the micellar size increased; and the zeta potential decreased. The DOX-CSO-SA micelles indicated pH-dependent DOX release behavior. The release rate of DOX from DOX-CSO-SA micelles increased significantly with the reductions of the pH for release medium from 7.2 to 5.0. In vitro antitumor activity tests of DOX-CSO-SA micelles against human breast carcinoma (MCF-7) cells and their multi-drug resistant (MCF-7/Adr) cells presented the reversal activity against DOX resistance MCF-7 cells (MCF-7/Adr). The in vivo antitumor activity results showed that DOX-CSO-SA micelles treatments effectively suppressed the tumor growth and reduced the toxicity against animal body than commercial doxorubicin hydrochloride injection. (C) 2009 Elsevier Ltd. All rights reserved.