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 Citations (Scopus)

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
StatePublished - Mar 1 2016

Fingerprint

Eukaryotic Initiation Factors
Catechin
Cell growth
RNA
Urinary Bladder Neoplasms
Nanoparticles
Small Interfering RNA
Tumors
Cats
Growth
Nanocomposites
Neoplasms
Gene therapy
Chemotherapy
Phosphatidylinositol 3-Kinases
Biocompatibility
Rats
Tea
Therapeutics
Oncogenes

Keywords

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

ASJC Scopus subject areas

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

Cite this

Mg(II)-Catechin nanoparticles delivering siRNA targeting EIF5A2 inhibit bladder cancer cell growth in vitro and in vivo. / Chen, Zhenhua; Yu, Ting; Zhou, Bangfen; Wei, Jinhuan; Fang, Yong; Lu, Jun; Guo, Ling; Chen, Wei; Liu, Zhi Ping; Luo, Junhang.

In: Biomaterials, Vol. 81, 01.03.2016, p. 125-134.

Research output: Contribution to journalArticle

Chen, Zhenhua ; Yu, Ting ; Zhou, Bangfen ; Wei, Jinhuan ; Fang, Yong ; Lu, Jun ; Guo, Ling ; Chen, Wei ; Liu, Zhi Ping ; Luo, Junhang. / Mg(II)-Catechin nanoparticles delivering siRNA targeting EIF5A2 inhibit bladder cancer cell growth in vitro and in vivo. In: Biomaterials. 2016 ; Vol. 81. pp. 125-134.
@article{fdec92b54cde4f1da17f198954cd12fd,
title = "Mg(II)-Catechin nanoparticles delivering siRNA targeting EIF5A2 inhibit bladder cancer cell growth in vitro and in vivo",
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.",
keywords = "Bladder cancer, EIF5A2, Gene therapy, Mg(II)-Catechin, Nanocomposite",
author = "Zhenhua Chen and Ting Yu and Bangfen Zhou and Jinhuan Wei and Yong Fang and Jun Lu and Ling Guo and Wei Chen and Liu, {Zhi Ping} and Junhang Luo",
year = "2016",
month = "3",
day = "1",
doi = "10.1016/j.biomaterials.2015.11.022",
language = "English (US)",
volume = "81",
pages = "125--134",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Mg(II)-Catechin nanoparticles delivering siRNA targeting EIF5A2 inhibit bladder cancer cell growth in vitro and in vivo

AU - Chen, Zhenhua

AU - Yu, Ting

AU - Zhou, Bangfen

AU - Wei, Jinhuan

AU - Fang, Yong

AU - Lu, Jun

AU - Guo, Ling

AU - Chen, Wei

AU - Liu, Zhi Ping

AU - Luo, Junhang

PY - 2016/3/1

Y1 - 2016/3/1

N2 - 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.

AB - 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.

KW - Bladder cancer

KW - EIF5A2

KW - Gene therapy

KW - Mg(II)-Catechin

KW - Nanocomposite

UR - http://www.scopus.com/inward/record.url?scp=84953290173&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84953290173&partnerID=8YFLogxK

U2 - 10.1016/j.biomaterials.2015.11.022

DO - 10.1016/j.biomaterials.2015.11.022

M3 - Article

C2 - 26731576

AN - SCOPUS:84953290173

VL - 81

SP - 125

EP - 134

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -