Multimerized self-assembled caged two-in-one siRNA nanoparticles for photomodulation of RNAi-induced gene silencing |
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Authors: | Changmai Chen Nannan Jing Zhongyu Wang Yu Zhang Wei Chen Xinjing Tang |
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Institution: | School of Pharmacy, Fujian Medical University, Fuzhou 350122 China ; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191 China, |
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Abstract: | We rationally designed and developed caged siRNA nanoparticles (Multi-Chol-siRNA) self-assembled with cholesterol-modified multimerized caged siRNAs for photomodulation of siRNA gene silencing activity. Strong resistance to serum nuclease and RNase A was observed for these cholesterol-modified caged siRNA nanoparticles due to the formation of nanostructures with high intensity of siRNA. These caged Multi-Chol-siRNA self-assembled nanoparticles were successfully used to achieve photochemical regulation of both exogenous GFP and endogenous Eg5 gene expressions with a GFP/RFP transient transfection system and Eg5-associated assays, respectively. Further, Two-in-One caged Multi-Chol-siGFP/siEg5 self-assembled nanoparticles simultaneously targeting GFP and Eg5 genes were also developed. The caged Multi-Chol-siRNA self-assembled nanoparticles have demonstrated the effectiveness of enhancing photomodulation of multiple RNAi-induced gene silencing activities in cells.Upon light irradiation, multimerized self-assembled caged Two-in-One siRNA nanoparticles (Multi-Chol-siRNA) were collapsed to release trapped siRNAs for multiple RNAi-induced gene silencing activity. |
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