title: Anti-tumor effects in mice induced by survivin-targeted siRNA delivered through polysaccharide nanoparticles.
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(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(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.
authors: 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.
authors: Feifei
authors: F
authors: Yang
authors: Wei
authors: W
authors: Huang
authors: Yunfei
authors: Y
authors: Li
authors: Shan
authors: S
authors: Liu
authors: Mingji
authors: M
authors: Jin
authors: Yuli
authors: Y
authors: Wang
authors: Lihua
authors: L
authors: Jia
authors: Zhonggao
authors: Z
authors: Gao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry*; D015536:Down-Regulation / Q000187:drug effects; D024202:Electrophoretic Mobility Shift Assay; D004705:Endocytosis; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D010316:Particle Size; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared; D000077022:Survivin; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D010455:Peptides; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000077022:Survivin; D048271:Chitosan; D008156:Luciferases