Preparation of poly(glutamic acid) shielding micelles self-assembled from polylysine-b-polyphenylalanine for gene and drug codelivery |
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| Institution: | 1. School of Materials Science and Engineering, Changchun University of Science and Technology, Changchun 130022, China;2. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China;1. State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, PR China;2. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, PR China;3. University of Science and Technology of China, Hefei, Anhui, 230026, PR China;4. University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, 100049, PR China;5. Department of Chemistry, University of Gujrat, Gujrat, 50700, Pakistan;1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China;2. University of Science and Technology of China, Hefei, Anhui, 230026, China;3. Jilin Biomedical Polymers Engineering Laboratory, Changchun, Jilin, 130022, China;1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China;2. University of Science and Technology of China, Hefei 230026, China;3. Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China;4. Department of Life Science and Technology, Tokyo Institute of Technology, Nagatsuta, Midori, Yokohama 226-8501, Japan;1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China;2. Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Cytology and Genetics, Northeast Normal University, Changchun 130024, China;3. Department of Microbiology and Molecular Genetics, University of the Punjab, 54590 Lahore, Pakistan;1. Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China;2. University of Chinese Academy of Sciences, Beijing 100049, PR China |
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| Abstract: | A novel amphiphilic cationic block copolymer polylysine-b-polyphenylalanine(PLL-b-PPhe) was synthesized and self-assembled into micelles in aqueous solution,then shielded with poly(glutamic acid)(marked as PG/PLL-b-PPhe) to codeliver gene and drug for combination cancer therapy.Here,doxorubicin(DOX) was selected to be loaded into PLL-b-PPhe micelles and the drug loading efficiency was 8.0%.The drug release studies revealed that the PLL-b-PPhe micelles were pH sensitive and the released DOX could reach to 53.0%,65.0%,72.0% at pH 7.4,6.8 and 5.0,respectively.In order to reduce positive charge and cytotoxicity of PLL-b-PPhe micelles,PG was used as shelding,simultaneously condensed with Bcl2 siRNA to form gene carrier system.Compared with PEI,PG/PLL-b-PPhe had excellent gene transfection efficiency,especially when the molar ratio of PLL to PPhe was 30:60 and the mixed mass ratio of PLL-b-PPhe to gene was 5:1.More importantly,DOX and Bcl2 siRNA gene codelivery system displayed remarkable cytotoxicity against B16 F10 cells.Confocal laser scanning microscopy(CLSM) and flow cytometry were used to characterize endocytosis of the codelivery system,and confirmed that both DOX and Bcl2 siRNA had been endocytosed into B16 F10 cells.The above results indicated that gene and drug codelivery was a promising strategy in future cancer therapy. |
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| Keywords: | Codelivery Shielding Doxorubicin Bcl2 siRNA Cancer therapy |
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