Dual pH-sensitive micelles with charge-switch for controlling cellular uptake and drug release to treat metastatic breast cancer
Dual pH-sensitive micelles with charge-switch for controlling cellular uptake and drug release to treat metastatic breast cancer
复制标题
具有电荷开关的双 pH 敏感胶束，用于控制细胞摄取和药物释放，以治疗转移性乳腺癌
DOI：
10.1016/j.biomaterials.2016.06.005
复制
发表时间：
2017-01-01
期刊：
影响因子：
14
通讯作者：
Li, Yaping
中科院分区：
文献类型：
--
作者：
Tang, Shan;Meng, Qingshuo;Li, Yaping
为了成功地对转移性乳腺癌进行化疗，仍然需要做出巨大努力来设计药物递送系统，该药物递送系统可以被肿瘤细胞选择性地内化并以受控的方式释放货物。在这项工作中，化疗药物紫杉醇（PTX）负载双pH敏感胶束（CMC），它由一个pH敏感的核心，酸可切割的阴离子外壳，和聚乙二醇（PEG）冠。在肿瘤组织的微酸性环境中，阴离子壳被去除，诱导PTX的表面电荷由负向正转化，这导致PTX在小鼠乳腺癌4 T1荷瘤小鼠模型中的更有效的细胞摄取、更强的细胞毒性和更高的肿瘤内蓄积，与具有不可去除的阴离子或非离子壳的胶束相比。同时，pH敏感的核心赋予了药物在内/溶酶体中的快速释放。结果表明，雷公藤多甙对肿瘤生长和肺转移的抑制率分别为77.7%和88.3%，无明显毒副作用。因此，由于既能满足肿瘤细胞的选择性摄取，又能满足细胞内药物充分快速释放的要求，因此有望成为一种有效治疗转移性乳腺癌的纳米载体。(C)2016爱思唯尔有限公司版权所有。
For successful chemotherapy against metastatic breast cancer, the great efforts are still required for designing drug delivery systems that can be selectively internalized by tumor cells and release the cargo in a controlled manner. In this work, the chemotherapeutic agent paclitaxel (PTX) was loaded with the dual-pH sensitive micelle (DPM), which consisted of a pH-sensitive core, an acid-cleavable anionic shell, and a polyethylene glycol (PEG) corona. In the slightly acidic environment of tumor tissues, the anionic shell was taken off, inducing the conversion of the surface charge of DPM from negative to positive, which resulted in more efficient cellular uptake, stronger cytotoxicity and higher intra-tumor accumulation of PTX in the murine breast cancer 4T1 tumor-bearing mice models compared to the micelles with irremovable anionic or non-ionic shell. Meanwhile, the pH-sensitive core endowed DPM with rapid drug release in endo/lysosomes. The inhibitory rates of DPM against tumor growth and lung metastasis achieved 77.7% and 88.3%, respectively, without significant toxicity. Therefore, DPM is a promising nanocarrier for effective therapy of metastatic breast cancer due to satisfying the requirements of both selective uptake by tumor cells and sufficient and fast intracellular drug release. (C) 2016 Elsevier Ltd. All rights reserved.