Reversal of multidrug resistance by mitochondrial targeted self-assembled nanocarrier based on stearylamine.

TitleReversal of multidrug resistance by mitochondrial targeted self-assembled nanocarrier based on stearylamine.
Publication TypeJournal Article
Year of Publication2013
AuthorsZhang Z, Liu Z, Ma L, Jiang S, Wang Y, Yu H, Yin Q, Cui J, Li Y
JournalMolecular pharmaceutics
Volume10
Issue6
Pagination2426-34
Date Published2013 Jun 3
Abstract

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 ± 3.43 nm) with a high encapsulation efficiency (99.25 ± 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.

DOI10.3978/j.issn.2225-319X.2013.07.23
Alternate JournalMol. Pharm.