Biocompatible gelatin nanoparticles for tumor-targeted delivery of polymerized siRNA in tumor-bearing mice
- Authors
- Lee, So Jin; Yhee, Ji Young; Kim, Sun Hwa; Kwon, Ick Chan; Kim, Kwangmeyung
- Issue Date
- 28-Nov-2013
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Gelatin; Nanoparticles; Polymerized siRNA; siRNA delivery system; Tumor-targeted delivery
- Citation
- JOURNAL OF CONTROLLED RELEASE, v.172, no.1, pp.358 - 366
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF CONTROLLED RELEASE
- Volume
- 172
- Number
- 1
- Start Page
- 358
- End Page
- 366
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/101557
- DOI
- 10.1016/j.jconrel.2013.09.002
- ISSN
- 0168-3659
- 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 mu g/ml psi-tGel NPs, which included 1 mu M 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. (C) 2013 Elsevier B. V. All rights reserved.
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Collections - Graduate School > KU-KIST Graduate School of Converging Science and Technology > 1. Journal Articles
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