Yinan Zhao1, Shubiao Zhang2, Yuan Zhang3, Shaohui Cui2, Huiying Chen2, Defu Zhi2, Yuhong Zhen4, Shufen Zhang5, Leaf Huang6. 1. State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116021, Liaoning, China ; SEAC-ME Key Laboratory of Biotechnology and Bio-resources Utilization, Dalian Nationalities University, Dalian 116600, Liaoning, China. 2. SEAC-ME Key Laboratory of Biotechnology and Bio-resources Utilization, Dalian Nationalities University, Dalian 116600, Liaoning, China. 3. Department of Materials Science and Engineering, Department of Biological Engineering, The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. 4. College of Phamacy, Dalian Medical University, Dalian 116044, Liaoning, China. 5. State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116021, Liaoning, China. 6. Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Abstract
Several novel tri-peptide cationic lipids were designed and synthesized for delivering DNA and siRNA. They have tri-lysine and tri-ornithine as head groups, carbamate group as linker and 12 and 14 carbon atom alkyl groups as tails. These tri-peptide cationic lipids were prepared into cationic liposomes for the study of the physicochemical properties and gene delivery. Their particle size, Zeta potential and DNA-binding were characterized to show that they were suitable for gene transfection. The further results indicate that these lipids can transfer DNA and siRNA very efficiently into NCI-H460 and Hep-2 tumor cells. The selected lipid, CDO14, was able to deliver combined siRNAs against c-Myc and VEGF for silencing distinct oncogenic pathways in lung tumors of mice, with little in vitro and in vivo toxicity.
Several novel tri-peptide cationic n>an class="Chemical">lipids were designed and synthesized for delivering DNA and siRNA. They have tri-lysine and tri-ornithine as head groups, carbamate group as linker and 12 and 14 carbon atom alkyl groups as tails. These tri-peptide cationic lipids were prepared into cationic liposomes for the study of the physicochemical properties and gene delivery. Their particle size, Zeta potential and DNA-binding were characterized to show that they were suitable for gene transfection. The further results indicate that these lipids can transfer DNA and siRNA very efficiently into NCI-H460 and Hep-2tumor cells. The selected lipid, CDO14, was able to deliver combined siRNAs against c-Myc and VEGF for silencing distinct oncogenic pathways in lung tumors of mice, with little in vitro and in vivo toxicity.
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