Tumor homing nanoparticles for siRNA delivery

Tumor homing nanoparticles for siRNA delivery
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Gene expression control by the small interfering RNA (siRNA) is a most promising tool for disease therapy by sequence specific cleavage of mRNA. The highly efficient and specific gene silencing by RNAi is applicable to all classes of molecular targets as a powerful new therapeutic agent that reduces or degrades undesirable mRNA. Though siRNA has a 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 systemic circulation. So, it requires safe and effective siRNA delivery system to improve siRNA function. Several viral and non-viral delivery strategies have been proposed to improve siRNA delivery, but their applications in vivo are still uncertain. Glycol chitosan based nanoparticles were reported as distinguished biocompatibility, biodegradability and tumor-targeting ability in cell culture system and tumor-bearing mice. Here we introduced nano-sized tumor-homing polymeric nanoparticels (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. Cleavable poly-siRNA was successfully synthesized and showed enhanced RNAi properties. By introducing the noninvasive optical fluorescence imaging technology, it is monitored the behaviors of siRNA-NP, like 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 for novel cancer therapeutic strategy.
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