Amphiphilic polycarbonate conjugates of doxorubicin with pH-sensitive hydrazone linker for controlled release
Amphiphilic polycarbonate conjugates of doxorubicin with pH-sensitive hydrazone linker for controlled release
复制标题
用于控制释放的阿霉素与 pH 敏感腙连接体的两亲性聚碳酸酯缀合物
DOI：
10.1016/j.colsurfb.2013.06.054
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发表时间：
2013-11-01
影响因子：
5.8
通讯作者：
Zhuo, Ren-Xi
中科院分区：
文献类型：
--
作者：
Jiang, Tao;Li, You-Mei;Zhuo, Ren-Xi
成功设计并合成了新型两亲性聚碳酸酯-多柔比星（mPEG-b-P(ATMC-co-DTC)-g-DOX），用于ph触发癌细胞细胞间药物释放。以固定化猪胰腺脂肪酶（IPPL）为催化剂，批量合成了两亲性嵌段共聚物mPEG-b-P（ATMC-co-DTC）。在ATMC单元烯丙基环氧化后，DOX通过腙键与疏水聚碳酸酯块共价结合。制备的mPEG-b-P(ATMC-co-DTC)-g-DOX前药可在水溶液中自组装形成纳米级胶束，疏水核中DOX含量分别为9.9和12.5 wt.%。在酸性介质中，由于DOX和聚碳酸酯之间具有酸可切割的腙键，从前药胶束中释放DOX的速度增加。MTT试验表明，本研究中DOX前药胶束对HeLa细胞具有有效的细胞毒作用。此外，共聚焦激光扫描显微镜（CLSM）观察还显示，mPEG-b-P(ATMC-co-DTC)-g-DOX前药可以有效地将DOX传递并释放到HeLa细胞的细胞核中。(C) 2013 Elsevier B.V.版权所有
Novel amphiphilic polycarbonates-graft-doxorubicin (mPEG-b-P(ATMC-co-DTC)-g-DOX) were successfully designed and synthesized for pH-triggered intercellular drug release in cancer cells. The amphiphilic block copolymer, mPEG-b-P(ATMC-co-DTC), was synthesized in bulk using immobilized porcine pancreas lipase (IPPL) as the catalyst. After allyl epoxidation of ATMC units, DOX was covalently conjugated to the hydrophobic polycarbonates block through a hydrazone linkage. The resulting mPEG-b-P(ATMC-co-DTC)-g-DOX prodrugs could self-assemble to form nano-sized micelles in aqueous solution, while DOX contents in the hydrophobic core were 9.9 and 12.5 wt.%. DOX release rate from the prodrug micelles increased in acidic medium due to the acid-cleavable hydrazone linkage between the DOX and polycarbonates. MTT assays demonstrated that DOX prodrug micelles in this study showed effective cytotoxic effects to HeLa cells. Furthermore, confocal laser scanning microscopy (CLSM) observations also revealed that mPEG-b-P(ATMC-co-DTC)-g-DOX prodrugs could efficiently deliver and release DOX into the nuclei of HeLa cells. (C) 2013 Elsevier B.V. All rights reserved.