A TPGS-incorporating nanoemulsion of paclitaxel circumvents drug resistance in breast cancer
A TPGS-incorporating nanoemulsion of paclitaxel circumvents drug resistance in breast cancer
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含有 TPGS 的紫杉醇纳米乳剂可避免乳腺癌的耐药性
DOI：
10.1016/j.ijpharm.2014.05.039
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发表时间：
2014-08-25
影响因子：
5.8
通讯作者：
Li, Yaping
中科院分区：
文献类型：
--
作者：
Bu, Huihui;He, Xinyu;Li, Yaping
紫杉醇耐药通常在临床化疗中产生，这仍然是成功治疗癌症的主要障碍。在此，我们试图开发一种TPGS掺入紫杉醇纳米乳剂（NE-PTX），以规避乳腺癌的耐药性。采用自组装技术制备了NE-PTX，并对其理化性质进行了表征。通过体外和体内评价来测量NE-PTX克服紫杉醇耐药性的功效。测量结果表明，NE-PTX是纳米尺寸的液滴，平均直径为24.93 +/- 3.45 nm。紫杉醇对耐药MCF-7/ADR细胞的IC 50值由101.45 mg/mL降至5.39 mg/mL，表明NE-PTX能有效降低MCF-7/ADR细胞对紫杉醇的耐药性。紫杉醇耐药逆转的主要机制可能是P-gp活性的显著抑制和抗癌活性的增强。NE-PTX治疗耐药裸鼠移植瘤模型的肿瘤体积仅为紫杉醇溶液组的10.06%，抑瘤率达93.84%，有效验证了NE-PTX治疗紫杉醇耐药的疗效。因此，NE-PTX可以提供一种有效的策略，以规避紫杉醇耐药的乳腺癌。(C)2014年爱思唯尔B。V.保留所有权利。
Paclitaxel resistance is usually developed in clinical chemotherapy, which remains a major obstacle for successful cancer treatment. Herein, we attempted to develop a TPGS incorporating nanoemulsion of paclitaxel (NE-PTX) to circumvent the drug resistance in breast cancer. NE-PTX was prepared by a self-assembly technique and the physicochemical properties were characterized. The efficacy of NE-PTX on overcoming paclitaxel resistance was measured by in vitro and in vivo evaluation. The measured results indicated that NE-PTX was nanometer-sized droplets with the mean diameter of 24.93 +/- 3.45 nm. The IC50 value of paclitaxel in resistant MCF-7/ADR cells was greatly reduced from 101.45 mg/mL to 5.39 mg/mL, which indicated that the paclitaxel resistance was effectively reduced by NE-PTX. The reversal of paclitaxel resistance could mainly ascribe to the significant inhibition of P-gp activity and enhancement of anti-cancer activity. Moreover, the tumor volume in resistant tumor xenograft model treated with NE-PTX was only 10.06% of that of paclitaxel solution group, and the tumor inhibitory rate of NE-PTX reached 93.84%, which effectively verified the efficacy of NE-PTX on treating paclitaxel resistance. Thereby, NE-PTX could provide an effective strategy for circumventing paclitaxel resistance in breast cancer. (C) 2014 Elsevier B. V. All rights reserved.