Co-delivery of VEGF and Bcl-2 dual-targeted siRNA polymer using a single nanoparticle for synergistic anti-cancer effects in vivo

So Jin Lee, Simmyung Yook, Ji Young Yhee, Hong Yeol Yoon, Myung Goo Kim, Sook Hee Ku, Sun Hwa Kim, Jae Hyung Park, Ji Hoon Jeong, Ick Chan Kwon, Seulki Lee, Hyukjin Lee, Kwangmeyung Kim

Research output: Contribution to journalArticle

Abstract

Cancer is a multifactorial disease which involves complex genetic mutation and dysregulation. Combinatorial RNAi technology and concurrent multiple gene silencing are expected to provide advanced strategies for effective cancer therapy, but a safe and effective carrier system is a prerequisite to successful siRNA delivery in vivo. We previously developed an effective tumor-targeting siRNA delivery system for in vivo application. In response to the success of this development, herein we present a dual-gene targeted siRNA and its delivery system, to achieve synergistic effects in cancer therapy. Two different sequences of siRNA were chemically modified to be randomly copolymerized in a single backbone of siRNA polymer (Dual-poly-siRNA), and the resulting Dual-poly-siRNA was incorporated into tumor-homing glycol chitosan nanoparticles. Based on the stability in serum and delivery in a tumor-targeted manner, intravenously administered Dual-poly-siRNA carrying glycol chitosan nanoparticles (Dual-NP) demonstrated successful dual-gene silencing in tumors. Notably, co-delivery of VEGF and Bcl-2 targeting siRNA led to more effective cancer therapy for convenient application.

Original languageEnglish (US)
Pages (from-to)631-641
Number of pages11
JournalJournal of Controlled Release
Volume220
DOIs
StatePublished - Dec 28 2015

Fingerprint

Nanoparticles
Vascular Endothelial Growth Factor A
Small Interfering RNA
Polymers
Neoplasms
Gene Silencing
RNA Interference
Therapeutics
Technology
Mutation
Serum
Genes

Keywords

  • Dual-gene delivery
  • Glycol chitosan
  • Nanoparticle
  • siRNA polymer
  • Tumor targeted delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Co-delivery of VEGF and Bcl-2 dual-targeted siRNA polymer using a single nanoparticle for synergistic anti-cancer effects in vivo. / Lee, So Jin; Yook, Simmyung; Yhee, Ji Young; Yoon, Hong Yeol; Kim, Myung Goo; Ku, Sook Hee; Kim, Sun Hwa; Park, Jae Hyung; Jeong, Ji Hoon; Kwon, Ick Chan; Lee, Seulki; Lee, Hyukjin; Kim, Kwangmeyung.

In: Journal of Controlled Release, Vol. 220, 28.12.2015, p. 631-641.

Research output: Contribution to journalArticle

Lee, SJ, Yook, S, Yhee, JY, Yoon, HY, Kim, MG, Ku, SH, Kim, SH, Park, JH, Jeong, JH, Kwon, IC, Lee, S, Lee, H & Kim, K 2015, 'Co-delivery of VEGF and Bcl-2 dual-targeted siRNA polymer using a single nanoparticle for synergistic anti-cancer effects in vivo', Journal of Controlled Release, vol. 220, pp. 631-641. https://doi.org/10.1016/j.jconrel.2015.08.032
Lee, So Jin ; Yook, Simmyung ; Yhee, Ji Young ; Yoon, Hong Yeol ; Kim, Myung Goo ; Ku, Sook Hee ; Kim, Sun Hwa ; Park, Jae Hyung ; Jeong, Ji Hoon ; Kwon, Ick Chan ; Lee, Seulki ; Lee, Hyukjin ; Kim, Kwangmeyung. / Co-delivery of VEGF and Bcl-2 dual-targeted siRNA polymer using a single nanoparticle for synergistic anti-cancer effects in vivo. In: Journal of Controlled Release. 2015 ; Vol. 220. pp. 631-641.
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