Non-invasive imaging of gene silencing efficacy of nano-sized siRNA delivery system in tumor-bearing mice

Non-invasive imaging of gene silencing efficacy of nano-sized siRNA delivery system in tumor-bearing mice
Issue Date
World molecular imaging conference
Molecular imaging technique is very useful to diagnosis of diverse diseases, such as cancer or inflammation, etc. So, we we Small interfering RNA (siRNA) therapy is good promising tool for treatment of diverse diseases, such as cancer and viral infection etc. But siRNA therapy has a hurdle for its’ clinical application due to low stability within physiological environment and poor cellular uptake efficiency. In this study, to overcome these problems, we designed a new nano-sized siRNA carrier system. We used siRNA for red fluorescent protein (RFP) gene, and synthesized it as a poly-siRNA (polymerized siRNA) mediated by disulfide bond at the 5′-ends of both sense and anti-sense strands of siRNA. For the efficient systemic delivery of poly-siRNA, biocompatible/biodegradable glycol chitosan polymer (GC) was introduced and modified, as a Thiolated GC. Thiolated GC was conjugated with poly-siRNA via disulfide bond. In vitro GC-poly-siRNA complexes exhibited good silencing efficiency to the RFP labeled melanoma cells (RFP/B16F10) compared to untreated cells, we confirm that using Kodak Image Station 4000MM Digital Imaging System. And GC-poly-siRNA presented a good targeting efficacy in vivo. In SCC7 tumor-bearing mice, GC-Cy 5.5 labeled poly-siRNA were intravenously injected and exhibit excellent tumor specificities and targeting of GC-Cy 5.5 labeled poly-siRNA were imaged by eXplore Optix System. Also we know GC-poly-siRNA locate in tumor tissuses. In tumors from mice administered GC-cy5.5 labeled-poly-siRNA, the cy5.5 siganal was observed in tissues outside of the vessels (FITC-dextran). Inhibition of RFP gene expression in RFP/B16F10-bearing mice is good efficacy, due to their higher tumor-targeting ability. These results revealed the promising therapeutic potential of Thiolated GC-poly-siRNA as a stable and effective nano-sized siRNA delivery system for cancer treatment .
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