Dual Tumor-Targeting Nanocarrier System for siRNA Delivery Based on pRNA and Modified Chitosan
| Autor: | Zhiyuan Wang, Nan Liu, Xingguo Mei, Siyu Ma, Shiqing Zhao, Yan Liu, Yue Gao, Min Zhang, Li Lin, Xuemei Tang, Cheng Liu, Xiujie Pan, Mingyuan Li, Yue Zhang, Xiaoqin Hu, Zhiping Li, Yu Wang, Yang Yang, Fanglin Yu, Hua Guan |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Tumor targeting Aptamer dual tumor-targeting nanocarrier system 02 engineering and technology Endocytosis folate Chitosan 03 medical and health sciences chemistry.chemical_compound Drug Discovery Gene silencing pRNA lcsh:RM1-950 aptamer 021001 nanoscience & nanotechnology Molecular biology 030104 developmental biology lcsh:Therapeutics. Pharmacology chemistry siRNA PEGylation Biophysics Molecular Medicine Original Article Delivery system Nanocarriers chitosan 0210 nano-technology |
| Zdroj: | Molecular Therapy. Nucleic Acids Molecular Therapy: Nucleic Acids, Vol 8, Iss, Pp 169-183 (2017) |
| ISSN: | 2162-2531 |
| Popis: | Highly specific and efficient delivery of siRNA is still unsatisfactory. Herein, a dual tumor-targeting siRNA delivery system combining pRNA dimers with chitosan nanoparticles (CNPPs) was designed to improve the specificity and efficiency of siRNA delivery. In this dual delivery system, folate-conjugated and PEGylated chitosan nanoparticles encapsulating pRNA dimers were used as the first class of delivery system and would selectively deliver intact pRNA dimers near or into target cells. pRNA dimers simultaneously carrying siRNA and targeting aptamer, the second class of delivery system, would specifically deliver siRNA into the target cells via aptamer-mediated endocytosis or proper particle size. To certify the delivering efficiency of this dual system, CNPPs, pRNA dimers alone, chitosan nanoparticles containing siRNA with folate conjugation and PEGylation (CNPS), and chitosan nanoparticles containing pRNA dimers alone (CN) were first prepared. Then, we observed that treatment with CNPPs resulted in increased cellular uptake, higher cell apoptosis, stronger cell cytotoxicity, and more efficacious gene silencing compared to the other three formulations. Higher accumulation of siRNA in the tumor site, stronger tumor inhibition, and longer circulating time were also observed with CNPPs compared to other formulations. In conclusion, this dual nanocarrier system showed high targeting and favorable therapeutic efficacy both in vitro and in vivo. Thereby, a new approach is provided in this study for specific and efficient delivery of siRNA, which lays a foundation for the development of pRNA hexamers, which can simultaneously carry six different substances. Keywords: dual tumor-targeting nanocarrier system, siRNA, chitosan, pRNA, folate, aptamer |
| Databáze: | OpenAIRE |
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