title: Reversal of multidrug resistance by mitochondrial targeted self-assembled nanocarrier based on stearylamine.
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.
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Zeying
authors.initials: Z
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Shijun
authors.initials: S
authors.lastname: Jiang
authors.forename: Yixin
authors.initials: Y
authors.lastname: Wang
authors.forename: Haijun
authors.initials: H
authors.lastname: Yu
authors.forename: Qi
authors.initials: Q
authors.lastname: Yin
authors.forename: Jingbin
authors.initials: J
authors.lastname: Cui
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
mesh_terms: D000588:Amines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D017207:Rats, Sprague-Dawley; D013713:Teniposide / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000588:Amines; D013713:Teniposide; C009317:stearylamine