Multiple siRNA delivery against cell cycle and anti-apoptosis proteins using lipid-substituted polyethylenimine in triple-negative breast cancer and nonmalignant cells
Manoj B. Parmar
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Search for more papers by this authorBárbara E. Arteaga Ballesteros
Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada
Search for more papers by this authorTimothy Fu
Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada
Search for more papers by this authorRemant Bahadur K.C.
Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada
Search for more papers by this authorHamidreza Montazeri Aliabadi
School of Pharmacy, Chapman University, Irvine, California, USA
Search for more papers by this authorJudith C. Hugh
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada
Search for more papers by this authorRaimar Löbenberg
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Search for more papers by this authorCorresponding Author
Hasan Uludağ
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada
Department of Biomedical Engineering, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
Correspondence to: H. Uludağ; 2−021 RTF, Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton AB T6G 2V2, Canada. E-mail: [email protected]Search for more papers by this authorManoj B. Parmar
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Search for more papers by this authorBárbara E. Arteaga Ballesteros
Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada
Search for more papers by this authorTimothy Fu
Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada
Search for more papers by this authorRemant Bahadur K.C.
Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada
Search for more papers by this authorHamidreza Montazeri Aliabadi
School of Pharmacy, Chapman University, Irvine, California, USA
Search for more papers by this authorJudith C. Hugh
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada
Search for more papers by this authorRaimar Löbenberg
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Search for more papers by this authorCorresponding Author
Hasan Uludağ
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada
Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton, Alberta, Canada
Department of Biomedical Engineering, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
Correspondence to: H. Uludağ; 2−021 RTF, Department of Chemical and Materials Engineering, Faculty of Engineering, University of Alberta, Edmonton AB T6G 2V2, Canada. E-mail: [email protected]Search for more papers by this authorAbstract
Conventional breast cancer therapies have significant limitations that warrant a search for alternative therapies. Short-interfering RNA (siRNA), delivered by polymeric biomaterials and capable of silencing specific genes critical for growth of cancer cells, holds great promise as an effective, and more specific therapy. Here, we employed amphiphilic polymers and silenced the expression of two cell cycle proteins, TTK and CDC20, and the anti-apoptosis protein survivin to determine the efficacy of polymer-mediated siRNA treatment in breast cancer cells as well as side effects in nonmalignant cells in vitro. We first identified effective siRNA carriers by screening a library of lipid-substituted polyethylenimines (PEI), and PEI substituted with linoleic acid (LA) emerged as the most effective carrier for selected siRNAs. Combinations of TTK/CDC20 and CDC20/Survivin siRNAs decreased the growth of MDA-MB-231 cells significantly, while only TTK/CDC20 combination inhibited MCF7 cell growth. The effects of combinational siRNA therapy was higher when complexes were formulated at lower siRNA:polymer ratio (1:2) compared to higher ratio (1:8) in nonmalignant cells. The lead polymer (1.2PEI-LA6) showed differential transfection efficiency based on the cell-type transfected. We conclude that the lipid-substituted polymers could serve as a viable platform for delivery of multiple siRNAs against critical targets in breast cancer therapy. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3031–3044, 2016.
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