Title |
siRNA-loaded selenium nanoparticle modified with hyaluronic acid for enhanced hepatocellular carcinoma therapy
|
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Published in |
International Journal of Nanomedicine, March 2018
|
DOI | 10.2147/ijn.s157519 |
Pubmed ID | |
Authors |
Yu Xia, Min Guo, Tiantian Xu, Yinghua Li, Changbing Wang, Zhengfang Lin, Mingqi Zhao, Bing Zhu |
Abstract |
Small interfering RNA (siRNA) as a new therapeutic modality holds promise for cancer treatment. However, the traditional viral carriers are prone to immunogenicity and risk of insertional mutagenesis. In order to provide a tumor-targeted delivery carrier of siRNA in cancer therapy, the hyaluronic acid (HA)-selenium (Se)-polyethylenimine (PEI) nanoparticle (NP) was fabricated by decorating SeNP with HA as a tumor-targeting moiety and by linking the polycationic polymers polyethylenimine PEI onto the surface of SeNP. The siRNA was loaded to the surface of SeNP HA-Se-PEI via the electrostatic interaction between siRNA and PEI to prepare the functionalized SeNP HA-Se-PEI@siRNA. The HA-Se-PEI@siRNA was internalized into the HepG2 cell mainly in a clathrin-mediated endocytosis manner. Owing to the active tumor-targeted effect mediated by HA, HA-Se-PEI@siRNA achieved the obvious higher transfection efficiency, greater gene silencing ability, and stronger cytotoxicity in the HepG2 cell compared with the passive tumor-targeted NP Se-PEI@siRNA. The knockdown of hairy and enhancer of split 5 by HA-Se-PEI@siRNA induced the HepG2 cell cycle arrest at the G0/G1 phase and apoptosis. Furthermore, the treatment with HA-Se-PEI@siRNA resulted in greater antitumor efficacy compared with the Se-PEI@siRNA in vitro and in vivo. In addition, the HA-Se-PEI@siRNA was almost no toxic to the key organs of mice. These findings provided an alternative therapeutic route for targeted cancer treatments. |
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Geographical breakdown
Country | Count | As % |
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Unknown | 51 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 11 | 22% |
Student > Ph. D. Student | 7 | 14% |
Researcher | 5 | 10% |
Student > Bachelor | 4 | 8% |
Student > Doctoral Student | 4 | 8% |
Other | 7 | 14% |
Unknown | 13 | 25% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 6 | 12% |
Chemistry | 5 | 10% |
Agricultural and Biological Sciences | 4 | 8% |
Other | 4 | 8% |
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