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Degradable Dextran Nanopolymer as a Carrier for Choline Kinase (ChoK) siRNA Cancer Therapy
Zhihang Chen1, Balaji Krishnamachary2, Zaver M Bhujwalla3
1JHU ICMIC Program, Division of Cancer Imaging Research, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. zchen19@jhu.edu.
Abstract:
Although small interfering RNA (siRNA) therapy has proven to be a specific and effective treatment in cells, the delivery of siRNA is a challenge for the applications of siRNA therapy. We present a degradable dextran with amine groups as an siRNA nano-carrier. In our nano-carrier, the amine groups are conjugated to the dextran platform through the acetal bonds, which are acid sensitive. Therefore this siRNA carrier is stable in neutral and basic conditions, while the amine groups can be cleaved and released from dextran platform under weak acid conditions (such as in endosomes). The cleavage and release of amine groups can reduce the toxicity of cationic polymer and enhance the transfection efficiency. We successfully applied this nano-carrier to deliver choline kinase (ChoK) siRNA for ChoK inhibition in cells.

