| Autor: |
Ubeda Gutierrez AM; Department of Biomedical Engineering, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada., Remant Bahadur KC; Department of Chemical & Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB T6G 2R3, Canada., Brandwein J; Department of Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, AB T6G 2R3, Canada., Uludağ H; Department of Chemical & Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, AB T6G 2R3, Canada.; Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2R3, Canada. |
| Abstrakt: |
We investigated the feasibility of using siRNA therapy for acute myeloid leukemia (AML) by developing macromolecular carriers that facilitated intracellular delivery of siRNA. The carriers were derived from low-molecular-weight (<2 kDa) polyethyleneimine (PEI) and modified with a range of aliphatic lipids. We identified linoleic acid and lauric acid-modified PEI as optimal carriers for siRNA delivery to AML cell lines KG1 and KG1a, as well as AML patient-derived mononuclear cells. As they have been proven to be potent targets in the treatment of AML, we examined the silencing of BCL2L12 and survivin and showed how it leads to the decrease in proliferation of KG1 and stem-cell-like KG1a cells. By optimizing the transfection schedule, we were able to enhance the effect of the siRNAs on proliferation over a period of 10 days. We additionally showed that with proper modifications of PEI, other genes, including MAP2K3 , CDC20 , and SOD-1 , could be targeted to decrease the proliferation of AML cells. Our studies demonstrated the versatility of siRNA delivery with modified PEI to elicit an effect in leukemic cells that are difficult to transfect, offering an alternative to conventional drugs for more precise and targeted treatment options. |
