pH-triggered intracellular release from actively targeting polymer micelles
pH-triggered intracellular release from actively targeting polymer micelles
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pH 触发主动靶向聚合物胶束的细胞内释放
DOI：
10.1016/j.biomaterials.2013.02.071
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发表时间：
2013-06-01
期刊：
影响因子：
14
通讯作者：
Zhou, Shaobing
中科院分区：
文献类型：
--
作者：
Guo, Xing;Shi, Chunli;Zhou, Shaobing
化疗被广泛应用于癌症患者的治疗，但其全身毒性大，疗效低，限制了其应用。纳米载体系统能够将其有毒的货物特异性地输送到癌细胞中，然后极大地克服这些缺点，引起了人们的广泛关注。在这里，我们开发了一种药物偶联胶束，将叶酸连接到DOX-偶联的聚乙二醇-聚己内酯上，以靶向肿瘤；DOX进一步与肼连接物(FA-HYD)连接，以实现pH触发的药物释放。与氨基甲酸酯(FA-CBM)或不含FA(m-HYD)的DOX偶联胶束相比，FA-HYD具有良好的生物相容性；通过Alamar蓝、流式细胞仪和激光共聚焦扫描显微镜(CLSM)分析，pH敏感的FA功能化的DOX偶联胶束具有更好的细胞摄取效率和对肿瘤细胞的更高的细胞毒性。体内药代动力学和生物分布研究表明，FA-HYD胶束显着延长了药物的血液循环时间，并使药物进入肿瘤组织而不是正常组织。体内抗肿瘤活性表明，FA-HYD胶束对人体的安全性最高，对肿瘤的治疗效果最好。因此，这种药物传递系统被认为是一种潜在的癌症治疗纳米载体。(C)2013爱思唯尔有限公司。保留所有权利。
Chemotherapy is widely applied to treat cancer patients but its application is limited due to the systemic toxicity and low efficacy. Nanocarrier system, which is capable of delivering their toxic cargos specifically into cancer cells and then greatly overcomes these disadvantages, has drawn a broad attention. Here we developed a drug-conjugated micelle for a better drug delivery in which folic acid was attached to the DOX-conjugated poly(ethylene glycol)-poly(epsilon-caprolactone) to target tumor; DOX was further connected with a hydrazone linker (FA-hyd) for a pH-triggered drug release. Comparing to other DOX-conjugated micelles either linked with carbamate (FA-cbm) or lacking FA(m-hyd), the developed FA-hyd demonstrated excellent biocompatibility; When analyzed with Alamar blue assays, flow cytometry and confocal laser scanning microscopy (CLSM), the pH-sensitive FA-functionalized DOX-conjugated micelles presented much better efficiency of cellular uptake and higher cytotoxicity to tumor cells. In vivo pharmacokinetics and biodistribution studies indicated that FA-hyd micelles significantly prolonged the blood circulation time of drug and enriched drug into the tumors rather than normal tissues. In vivo antitumor activity demonstrated that FA-hyd micelles had the highest safety to body and the best therapeutic efficacy to tumors. Therefore, this drug delivery system is deemed as a potential nanocarrier for cancer therapy. (C) 2013 Elsevier Ltd. All rights reserved.