Reversal of Multidrug Resistance by Mitochondrial Targeted Self-Assembled Nanocarrier Based on Stearylamine
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- 作者：Zhiwen Zhang ; Zeying Liu ; Li Ma ; Shijun Jiang ; Yixin Wang ; Haijun Yu ; Qi Yin ; Jingbin Cui ; Yaping Li
- 刊名：Molecular Pharmaceutics
- 出版年：2013
- 出版时间：June 3, 2013
- 年：2013
- 卷：10
- 期：6
- 页码：2426-2434
- 全文大小：458K
- 年卷期：v.10,no.6(June 3, 2013)
- ISSN：1543-8392
文摘
Multidrug resistance (MDR) remains one of the major challenges for successful chemotherapy. Herein, we tried to develope a mitochondria targeted teniposide loaded self-assembled nanocarrier based on stearylamine (SA-TSN) to reverse MDR of breast cancer. SA-TSN was nanometer-sized spherical particles (31.59 卤 3.43 nm) with a high encapsulation efficiency (99.25 卤 0.21%). The MDR in MCF-7/ADR cells was obviously reduced by SA-TSN, which mainly attributed to the markedly reduced expression of P-gp, increased percentages in G2 phase, selectively accumulation in mitochondria, decrease of mitochondrial membrane potential, and greatly improved apoptosis. The plasma concentration of teniposide was greatly improved by SA-TSN, and the intravenously administered SA-TSN could accumulate in the tumor site and penetrate into the inner site of tumor in MCF-7/ADR induced xenografts. In particular, the in vivo tumor inhibitory efficacy of SA-TSN in MCF-7/ADR induced models was more effective than that of teniposide loaded self-assembled nanocarrier without stearylamine (TSN) and teniposide solution (TS), which verified the effectiveness of SA-TSN in reversal of MDR. Thereby, SA-TSN has potential to circumvent the MDR for the chemotherapy of breast cancer.