Degradable Dextran Nanopolymer as a Carrier for Choline Kinase (ChoK) siRNA Cancer Therapy
نویسندگان
چکیده
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.
منابع مشابه
Acid-degradable Dextran as an Image Guided siRNA Carrier for COX-2 Downregulation
Purpose: Effective in vivo delivery of siRNA to silence genes is a highly sought-after goal in the treatment of multiple diseases. Cyclooxygenase-2 (COX-2) is a major mediator of inflammation and its effective and specific downregulation has been of major interest to treat conditions ranging from auto-immune diseases to gastric inflammation and cancer. Here we developed a novel and efficient me...
متن کاملSmall Molecule Therapeutics Direct Inhibition of Choline Kinase by a Near-Infrared Fluorescent Carbocyanine
Choline kinase alpha (ChoK) expression is increasingly being recognized as an important indicator of breast cancer prognosis; however, previous efforts to noninvasively measure ChoK status have been complicated by the spectral limitations of in vivomagnetic resonance spectroscopy (MRS) and the complex network of enzymes involved in choline metabolism. The most effective ChoK inhibitors are symm...
متن کاملDirect inhibition of choline kinase by a near-infrared fluorescent carbocyanine.
Choline kinase alpha (ChoK) expression is increasingly being recognized as an important indicator of breast cancer prognosis; however, previous efforts to noninvasively measure ChoK status have been complicated by the spectral limitations of in vivo magnetic resonance spectroscopy (MRS) and the complex network of enzymes involved in choline metabolism. The most effective ChoK inhibitors are sym...
متن کاملCholine kinase activation is a critical requirement for the proliferation of primary human mammary epithelial cells and breast tumor progression.
Breast cancer is still one of the most important tumors among women in industrialized countries. Improvement in both understanding the molecular events associated with the disease and the development of new additional treatments is still an important goal to be achieved. Choline kinase (ChoK) is increased in human mammary tumors with high incidence, and this activation is associated with clinic...
متن کاملValue of 11C-choline PET/CT for lung cancer diagnosis and the relation between choline metabolism and proliferation of cancer cells.
The aim of this study was to investigate the efficacy of 11C-choline PET/CT imaging for lung cancer and the correlation between choline uptake of lung cancer tissue and the expression of choline kinase (ChoK), phosphorylcholine-cytidyl transferase and Ki-67 index. Between March 2008 and June 2010, 53 patients diagnosed or suspected of having lung ...
متن کامل