Lee, So Jin Yhee, Ji Young Kim, Sun Hwa Kwon, Ick Chan Kim, Kwangmeyung 2024-01-20T11:02:52Z 2024-01-20T11:02:52Z 2021-09-05 2013-11-28 0168-3659 https://pubs.kist.re.kr/handle/201004/127423 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. English ELSEVIER SCIENCE BV DRUG-DELIVERY GENE DELIVERY CATIONIC LIPIDS GLUTATHIONE TOXICITY THERAPEUTICS STABILITY COMPLEXES EFFICACY THERAPY Biocompatible gelatin nanoparticles for tumor-targeted delivery of polymerized siRNA in tumor-bearing mice Article 10.1016/j.jconrel.2013.09.002 1 JOURNAL OF CONTROLLED RELEASE, v.172, no.1, pp.358 - 366 JOURNAL OF CONTROLLED RELEASE 172 1 358 366 scie scopus 000327601200040 2-s2.0-84884641829 Chemistry, Multidisciplinary Pharmacology & Pharmacy Chemistry Pharmacology & Pharmacy Article DRUG-DELIVERY GENE DELIVERY CATIONIC LIPIDS GLUTATHIONE TOXICITY THERAPEUTICS STABILITY COMPLEXES EFFICACY THERAPY Gelatin Nanoparticles Polymerized siRNA siRNA delivery system Tumor-targeted delivery