Biomaterials, July, 2013, Vol.34(22), p.5689(11)
To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.biomaterials.2013.03.047 Byline: Feifei Yang, Wei Huang, Yunfei Li, Shan Liu, Mingji Jin, Yuli Wang, Lihua Jia, Zhonggao Gao Abstract: Recently, survivin has been attracting great attention because it plays an important role in inhibiting the apoptosis process of tumor cells. Down-regulating the expression of survivin gene by small interfering RNA (siRNA) offers a promising method for anti-tumor therapy. However, lack of appropriate siRNA delivery vector has significantly hindered the successful application of survivin-targeted siRNA in anti-tumor therapy. The purpose of this study was to use polysaccharide vector TAT-g-CS we synthesized to deliver functional siRNA and evaluate its in vivo anti-tumor activity. TAT-g-CS vector was firstly synthesized and well structurally characterized. MTT assay showed that TAT-g-CS vector exhibited good biocompatibility. TAT-g-CS complexed with siRNA offering nanoparticles with an average particle size of 212.2 nm and a polydispersity index of 0.121, and the zeta potential of the nanoparticles was +18.58 mV. Results from reporter gene assay suggested that luciferase-targeted siRNA when delivered by TAT-g-CS could down-regulate the expression of luciferase gene with 75.3% reduction. Most importantly, we use siRNA.sup.Sur targeting survivin gene to assess the in vitro and in vivo delivery capacity of TAT-g-CS and its anti-tumor effects. Our results demonstrated that TAT-g-CS/siRNA.sup.Sur nanoparticles not only strongly inhibited the in vitro proliferation of 4T1-Luc tumor cells via inducing cell apoptosis, but also effectively inhibited the in vivo growth and metastasis of malignant breast tumor, which suggested that TAT-g-CS/siRNA nanoparticle was a highly efficient non-viral system for siRNA delivery, especially for anti-tumor therapy based on siRNA therapeutics. Author Affiliation: (a) State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China (b) Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China (c) Yanbian University, Yanji 133000, PR China (d) Beijing Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, PR China (e) 307 Hospital, PLA, Academy of Military Medical Sciences, Beijing 100071, PR China Article History: Received 21 February 2013; Accepted 15 March 2013
Polysaccharides ; Nanoparticles ; Tumors ; Rna ; Luciferase
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