Rolling circle transcription-based polymeric siRNA nanoparticles for tumor-targeted delivery

Jae Hyeop Lee, Sook Hee Ku, Min Ju Kim, So Jin Lee, Hyun Cheol Kim, Kwang Meyung Kim, Sun Hwa Kim, Ick Chan Kwon

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

RNA, one of the major biological macromolecules, has been considered as an attractive building material for bottom-up fabrication of nanostructures in the past few decades due to advancements in RNA biology, RNA chemistry and RNA nanotechnology. Most recently, an isothermal enzymatic nucleic acid amplification method termed rolling circle transcription (RCT), which achieves a large-scale synthesis of RNA nanostructures, has emerged as one of fascinating techniques for RNAi-based therapies. Herein, we proposed a newly designed RCT method for synthesis of polymeric siRNA nanoflower, referred to 'RCT and annealing-generated polymeric siRNA (RAPSI)': (1) Amplification of the antisense strand of siRNA via RCT process and (2) annealing of chimeric sense strand containing 3'-terminal DNA nucleotides that provide enzyme cleavage sites. To verify its potentials in RNAi-based cancer therapy, the newly designed RAPSI nanoflower was further complexed with glycol chitosan (GC) derivatives, and systemically delivered to PC-3 xenograft tumors. The resultant RAPSI nanoparticles exhibited the improved particle stability against polyanion competition or nuclease attack. When the RAPSI nanoparticles reached to the cytoplasmic region, active mono siRNA was liberated and significantly down-regulated the expression of target VEGF gene in PC-3 cells. Excellent tumor-homing efficacy and anti-tumor effects of the RAPSI nanoparticles were further demonstrated. Overall, the proposed RCT-based polymeric siRNA nanoflower formulation can provide a new platform technology that allows further functional modifications via an advanced annealing method for systemic cancer RNAi therapy.

Original languageEnglish
JournalJournal of Controlled Release
DOIs
Publication statusAccepted/In press - 2016 Dec 2

Fingerprint

Nanoparticles
Small Interfering RNA
Neoplasms
RNA
Nanostructures
Nanotechnology
Heterografts
Nucleic Acids
Vascular Endothelial Growth Factor A
Nucleotides
Technology
DNA
Enzymes
Genes
RNAi Therapeutics

Keywords

  • Glycol chitosan nanoparticle
  • Prostate cancer
  • RNA interference
  • Rolling circle transcription
  • VEGF

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Rolling circle transcription-based polymeric siRNA nanoparticles for tumor-targeted delivery. / Lee, Jae Hyeop; Ku, Sook Hee; Kim, Min Ju; Lee, So Jin; Kim, Hyun Cheol; Kim, Kwang Meyung; Kim, Sun Hwa; Kwon, Ick Chan.

In: Journal of Controlled Release, 02.12.2016.

Research output: Contribution to journalArticle

Lee, Jae Hyeop ; Ku, Sook Hee ; Kim, Min Ju ; Lee, So Jin ; Kim, Hyun Cheol ; Kim, Kwang Meyung ; Kim, Sun Hwa ; Kwon, Ick Chan. / Rolling circle transcription-based polymeric siRNA nanoparticles for tumor-targeted delivery. In: Journal of Controlled Release. 2016.
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