Enhancing Systemic Delivery of Enzymatically Generated RNAi Nanocomplexes for Cancer Therapy

Hyangsu Nam, Sook Hee Ku, Hong Yeol Yoon, Kwangmeyung Kim, Ick Chan Kwon, Sun Hwa Kim, Jong Bum Lee

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Despite the superb therapeutic potential of siRNA technology, its clinical application are still limited due to the inherent instability and lack of systemic delivery issues. Recently, the development of long-chain siRNA has been proposed as a strategy to improve in vivo stability, particularly for efficient physical integration of siRNA molecules into gene carriers. Herein, concatemeric siRNAs are enzymatically synthesized through a rolling circle transcription process, and form stable RNA interference (RNAi) nanocomplexes with a redox-sensitive glycol chitosan derivative to systemically deliver the concatemeric siRNAs to tumor tissues. The enzymatically generated RNAi nanocomplexes (RNCs) have higher particle stability and less cytotoxicity than the conventional polyelectrolyte complexes. The therapeutic potential of the RNC formulation is verified in vivo as well as in vitro using VEGF as an antiangiogenic target for RNAi-based anticancer therapy. After systemic administration, RNC is specifically accumulated in tumor tissues and shows a high inhibitory effect on tumor growth. According to the results, the RNC can be considered as a platform technology for efficient tumor-targeted siRNA delivery systems.

Original languageEnglish
Article number1900014
JournalAdvanced Therapeutics
Volume2
Issue number6
DOIs
Publication statusPublished - 2019 Jun
Externally publishedYes

Keywords

  • concatemeric siRNA
  • rolling circle transcription
  • structural modification
  • systemic siRNA delivery system
  • tumor-targeted delivery

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Pharmaceutical Science
  • Genetics(clinical)
  • Biochemistry, medical
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Enhancing Systemic Delivery of Enzymatically Generated RNAi Nanocomplexes for Cancer Therapy'. Together they form a unique fingerprint.

Cite this