Tumor-homing Nanoparticles for siRNA Delivery

Tumor-homing Nanoparticles for siRNA Delivery
siRNA; poly-siRNA; tumor-homing polymeric nanoparticles; gene silencing
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한국바이오칩학회, 나노메디슨분과 심포지움
Gene expression control by the small interfering RNA (siRNA) has been attracted as a most promising tool for disease therapy by sequence specific cleavage of mRNA. Though siRNA shows powerful potential to gene therapy due to its high efficiency and specificity, but its clinical application has a huddle for its low stability, poor cellular uptake and rapid clearance from the physiological condition. So, it requires safe and effective siRNA delivery system to improve siRNA function. Glycol chitosan based nanoparticles were reported as distinguished biocompatibility and tumor-homing ability in cell culture system and tumor-bearing mice. Here we introduced nano-sized tumor-homing polymeric nanoparticles (NP) for application of siRNA therapy which composed of glycol chitosan. Systemic administration of the biocompatible and biodegradable siRNA-NP into tumor bearing mice showed selective tumor uptake, and siRNA sequence-specific suppression of gene expression within the tumor tissue and inhibition of tumor growth. Also we designed reducible polymerized siRNA as a novel powerful approach for siRNA delivery. To overcome the low charge density of siRNA and structural defect to make nanoparticles, we introduced cleavable disulfide bond to the siRNA. The poly-siRNA was successfully synthesized and showed enhanced RNAi properties. By using the noninvasive optical fluorescence imaging technology, it was monitored the behaviors of siRNA-nanoparticles, such as tumor targeting efficacy, biodistribution of complexes and elucidate the gene silencing effects. From the development of siRNA delivery system and imaging technique, we will support the core platform technology of siRNA therapeutics and perform the novel cancer treatment using siRNA.
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