Targeting ETS1 with RNAi-based supramolecular nanoassemblies for multidrug-resistant breast cancer therapy

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

39 Scopus Citations
View graph of relations

Author(s)

  • Min Wu
  • Xingang Liu
  • Weihong Jin
  • Yongbing Li
  • Yang Li
  • Qinglian Hu
  • Guping Tang
  • Yuan Ping

Detail(s)

Original languageEnglish
Pages (from-to)110-121
Journal / PublicationJournal of Controlled Release
Volume253
Online published14 Mar 2017
Publication statusPublished - 10 May 2017

Abstract

Overexpression of erythroblastosis virus E26 oncogene homolog 1 (ETS1) gene is correlated with both tumor progression and poor response to chemotherapy in cancer treatment, and the exploitation of RNA interference (RNAi) technology to downregulate ETS1 seems to be a promising approach to reverse multidrug-resistant cancer cells to chemotherapy. Hence, the RNAi-based nanomedicine which is able to simultaneously downregulate ETS1 expression and to deliver chemotherapeutic agents may improve multidrug-resistant cancer therapy synergistically. In this study, we developed a supramolecular nanoassembly that could deliver siRNA targeting ETS1 (siETS1) and doxorubicin (DOX) as an effective nanomedicine to achieve successful chemotherapy towards multidrug-resistant breast cancer. The nanotherapeutic system was prepared by loading adamantane-conjugated doxorubicin (AD) into polyethyleneimine-modified (2-hydroxypropyl)-γ-cyclodextrin (HP) through the supramolecular assembly to form AD-loaded HP (HPAD), followed by electrostatically-driven self-assembly between siETS1 and HPAD. When the HPAD/siETS1 nanoassemblies were delivered into drug-resistant MCF-7/ADR cells, the drug efflux was significantly reduced as a result of simultaneous silencing of ETS1 and MDR1 genes. Importantly, the HPAD/siETS1 nanoassembly could enhance drug residence time at tumor site, and effectively inhibit drug-resistant tumor growth due to the inhibition of angiogenesis and necrosis in tumor tissues. Western blot analysis indicated that the gene expression of both ETS1 and MDR1 in vivo was considerably downregulated after the drug-resistant tumor-bearing mouse was treated with HPAD/siETS1 nanoassemblies. This study offers a new therapeutic delivery strategy targeting ETS1 for the effective multidrug-resistant chemotherapy.

Research Area(s)

  • Doxorubicin, Drug delivery, Erythroblastosis virus E26 oncogene homolog 1, Multidrug resistance, Nanomedicine, siRNA

Citation Format(s)

Targeting ETS1 with RNAi-based supramolecular nanoassemblies for multidrug-resistant breast cancer therapy. / Wu, Min; Liu, Xingang; Jin, Weihong et al.
In: Journal of Controlled Release, Vol. 253, 10.05.2017, p. 110-121.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review