TY - JOUR
T1 - Biocompatible gelatin nanoparticles for tumor-targeted delivery of polymerized siRNA in tumor-bearing mice
AU - Lee, So Jin
AU - Yhee, Ji Young
AU - Kim, Sun Hwa
AU - Kwon, Ick Chan
AU - Kim, Kwangmeyung
N1 - Funding Information:
This study was funded by the GiRC Project , the Fusion Technology Project (2010–50201), and the Intramural Research Program (Young Fellow Program) of KIST .
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Gelatin
KW - Nanoparticles
KW - Polymerized siRNA
KW - Tumor-targeted delivery
KW - siRNA delivery system
UR - http://www.scopus.com/inward/record.url?scp=84884641829&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2013.09.002
DO - 10.1016/j.jconrel.2013.09.002
M3 - Article
C2 - 24036198
AN - SCOPUS:84884641829
VL - 172
SP - 358
EP - 366
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 1
ER -