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一种简单的还原敏感型胶束共递送紫杉醇和达沙替尼以克服肿瘤多药耐药性。

A simple reduction-sensitive micelles co-delivery of paclitaxel and dasatinib to overcome tumor multidrug resistance.

作者信息

Li Jun, Xu Ruitong, Lu Xiao, He Jing, Jin Shidai

机构信息

Department of Medical Oncology.

Department of General Practice, The First Affiliated Hospital with Nanjing Medical University, Nanjing.

出版信息

Int J Nanomedicine. 2017 Nov 1;12:8043-8056. doi: 10.2147/IJN.S148273. eCollection 2017.

Abstract

Multidrug resistance (MDR) is one of the major obstacles in successful chemotherapy. The combination of chemotherapy drugs and multidrug-resistant reversing agents for treating MDR tumor is a good strategy to overcome MDR. In this work, we prepared the simple redox-responsive micelles based on mPEG-SS-C as a co-delivery system to load the paclitaxel (PTX) and dasatinib (DAS) for treatment of MCF-7/ADR cells. The co-loaded micelles had a good dispersity and a spherical shape with a uniform size distribution, and they could quickly disassemble and rapidly release drugs under the reduction environment. Compared with MCF-7 cells, the DAS and PTX co-loaded redox-sensitive micelle (SS-PDNPs) showed stronger cytotoxicity and a more improving intracellular drug concentration than other drug formulations in MCF-7/ADR cells. In summary, the results suggested that the simple co-delivery micelles of PTX and DAS possessed significant potential to overcome drug resistance in cancer therapy.

摘要

多药耐药性(MDR)是成功进行化疗的主要障碍之一。联合使用化疗药物和多药耐药逆转剂治疗多药耐药肿瘤是克服MDR的一种良好策略。在本研究中,我们制备了基于mPEG-SS-C的简单氧化还原响应性胶束作为共递送系统,用于负载紫杉醇(PTX)和达沙替尼(DAS)以治疗MCF-7/ADR细胞。共负载胶束具有良好的分散性,呈球形且尺寸分布均匀,并且在还原环境下能够快速拆解并迅速释放药物。与MCF-7细胞相比,共负载DAS和PTX的氧化还原敏感胶束(SS-PDNPs)在MCF-7/ADR细胞中表现出比其他药物制剂更强的细胞毒性以及更高的细胞内药物浓度。总之,结果表明PTX和DAS的简单共递送胶束在癌症治疗中具有克服耐药性的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6939/5677301/55dd2cb3f99a/ijn-12-8043Fig1.jpg

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