Nuclear-targeted siRNA delivery for long-term gene silencing.

Chem Sci 2017 Apr 19;8(4):2816-2822. Epub 2017 Jan 19.

College of Chemistry , Chemical Engineering and Materials Science , Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong , Key Laboratory of Molecular and Nano Probes , Ministry of Education , Institute of Molecular and Nano Science , Shandong Normal University , Jinan 250014 , P. R. China . Email:

Developing effective nonviral siRNA delivery systems for long-term gene silencing remains a great challenge. Here we present a nuclear-targeted siRNA delivery system that can induce long-term gene silencing in cancer cells. The nanocarrier consists of gold nanoparticles modified with a dense shell of synthetic siRNAs and nuclear localization signal (NLS) peptides. The NLS peptide could translocate the nanocarrier into the nucleus and the siRNA was designed to target the promoter of thymidine kinase 1 and trigger the RNA-directed DNA methylation, thereby enabling the nuclear-targeted gene silencing. Compared with traditional gene silencing in cytoplasm, long-lasting gene knockdown could be achieved for the nuclear-targeted nanocarrier, which lasts for more than 30 days. The long-term gene silencing induced by nuclear-targeted siRNA delivery could effectively inhibit the proliferation of cancer cells and prevent the formation of a tumor in a mouse model.

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http://dx.doi.org/10.1039/c6sc04293gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427680PMC
April 2017
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