Multimerized self-assembled caged two-in-one siRNA nanoparticles for photomodulation of RNAi-induced gene silencing

• Published in: Chemical science (Cambridge) Vol. 11; no. 45; pp. 12289 - 12297
• Main Authors: Chen, Changmai, Jing, Nannan, Wang, Zhongyu, Zhang, Yu, Chen, Wei, Tang, Xinjing
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 07.12.2020; The Royal Society of Chemistry
• Subjects: Chemistry; Cholesterol; Nanoparticles; Nuclease; Self-assembly
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d0sc03562a

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.