Biocompatible gelatin nanoparticles for tumor-targeted delivery of polymerized siRNA in tumor-bearing mice

So Jin Lee, Ji Young Yhee, Sun Hwa Kim, Ick Chan Kwon, Kwang Meyung Kim

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Structural modifications of the siRNA backbone improved its physiochemical properties for incorporating in gene carriers without loss of gene-silencing efficacy. These modifications provide a wider variety of choice of vector systems for siRNA delivery. We developed a tumor-targeted siRNA delivery system using polymerized siRNA (poly-siRNA) and natural polymer gelatin. The polymerized siRNA (poly-siRNA) was prepared through self-polymerization of thiol groups at the 5′-end of sense and anti-sense strands of siRNA and was encapsulated in the self-assembled thiolated gelatin (tGel) nanoparticles (NPs) with chemical cross-linking. The resulting poly-siRNA-tGel (psi-tGel) nanoparticles (average of 145 nm in diameter) protect siRNA molecules from enzymatic degradation, and can be reversibly reduced to release functional siRNA molecules in reductive conditions. The psi-tGel NPs presented efficient siRNA delivery in red fluorescence protein expressing melanoma cells (RFP/B16F10) to down-regulate target gene expression. In addition, the NPs showed low toxicity at a high transfection dose of 125 μg/ml psi-tGel NPs, which included 1 μM of siRNA molecules. In tumor-bearing mice, the psi-tGel NPs showed 2.8 times higher tumor accumulation than the naked poly-siRNA, suggesting tumor-targeted siRNA delivery of psi-tGel NPs. Importantly, the psi-tGel NPs induced effective tumor RFP gene silencing in vivo without remarkable toxicity. The psi-tGel NPs have great potential for a systemic siRNA delivery system for cancer therapy, based on their characteristics of low toxicity, tumor accumulation, and effective siRNA delivery.

Original languageEnglish
Pages (from-to)358-366
Number of pages9
JournalJournal of Controlled Release
Volume172
Issue number1
DOIs
Publication statusPublished - 2013 Oct 1

Fingerprint

Gelatin
Nanoparticles
Small Interfering RNA
Neoplasms
Gene Silencing

Keywords

  • Gelatin
  • Nanoparticles
  • Polymerized siRNA
  • siRNA delivery system
  • Tumor-targeted delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Biocompatible gelatin nanoparticles for tumor-targeted delivery of polymerized siRNA in tumor-bearing mice. / Lee, So Jin; Yhee, Ji Young; Kim, Sun Hwa; Kwon, Ick Chan; Kim, Kwang Meyung.

In: Journal of Controlled Release, Vol. 172, No. 1, 01.10.2013, p. 358-366.

Research output: Contribution to journalArticle

Lee, So Jin ; Yhee, Ji Young ; Kim, Sun Hwa ; Kwon, Ick Chan ; Kim, Kwang Meyung. / Biocompatible gelatin nanoparticles for tumor-targeted delivery of polymerized siRNA in tumor-bearing mice. In: Journal of Controlled Release. 2013 ; Vol. 172, No. 1. pp. 358-366.
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