Mg(II)-Catechin nanoparticles delivering siRNA targeting EIF5A2 inhibit bladder cancer cell growth in vitro and in vivo

Zhenhua Chen, Ting Yu, Bangfen Zhou, Jinhuan Wei, Yong Fang, Jun Lu, Ling Guo, Wei Chen, Zhi Ping Liu, Junhang Luo

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Emerging evidence indicates that combination of two or more therapeutic strategies can synergistically enhance antitumor activity in cancer therapy. Here, we established a green method of generating nanocomposite particles that can be fabricated using catechin, a natural anti-cancer compound from green tea, and Mg2+ in an easy one-step approach at room temperature. We show that Mg(II)-Catechin nanocomposite particles (Mg(II)-Cat NPs) have good biocompatibility and high cellular uptake also can load and effectively deliver small interfering RNA (siRNA) into cells in vitro and to tumor site in vivo. Mg(II)-Cat NPs by themselves had tumor-suppression effects. When complexed with siRNA that targets oncogene eukaryotic translation initiation factor 5A2 (EIF5A2), Mg(II)-Cat/siEIF5A2 complex had further enhanced anti-tumor activity. Mechanistically, we show that Mg(II)-Cat/siEIF5A2 inhibits oncogenic PI3K/Akt signal pathway. More importantly, Mg(II)-Cat/siEIF5A2 had tumor suppression effect in a clinically-relevant rat in-situ bladder cancer model. Our studies demonstrated that combination of Mg(II)-Cat NPs and siRNA is a promising therapeutic modality of combining chemotherapy with gene therapy in order to afford higher therapeutic efficacy and provided a proof of principle for such modality in a pre-clinical setting.

Original languageEnglish (US)
Pages (from-to)125-134
Number of pages10
JournalBiomaterials
Volume81
DOIs
Publication statusPublished - Mar 1 2016

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Keywords

  • Bladder cancer
  • EIF5A2
  • Gene therapy
  • Mg(II)-Catechin
  • Nanocomposite

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

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