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通过靶向 Gli 1 递送拥有新基因载体的 siRNA 用于神经胶质瘤治疗
Authors Zhou P, Cao Y, Liu X, Yu T, Xu Q, You C, Gao X, Wei Y
Received 2 February 2018
Accepted for publication 15 May 2018
Published 27 August 2018 Volume 2018:13 Pages 4781—4793
DOI https://doi.org/10.2147/IJN.S164364
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Alexander Kharlamov
Peer reviewer comments 5
Editor who approved publication: Prof. Dr. Thomas J Webster
Background: Gene therapy has recently shown considerable clinical benefit in cancer therapy during the past few years, and the application of this choice in cancer treatments is increasing continually. Gli 1 is an ideal candidate target for cancer gene therapy and is important for tumorigenesis.
Methods: In this study, we developed a novel gene delivery system with a self-assembly method by using a 1,2-dioleoyl-3-trimethylammonium-propane and methoxy poly (ethylene glycol)-poly(lactide) copolymer (DMP), with zeta potential of 32.7 mV and measuring 35.6 nm. The effect of this delivery system was tested in vitro and in vivo.
Results: DMP showed good performance in delivering siRNA to glioma cells in vitro with high transfection performance (98%). Moreover, DMP–Gli 1 si shows a satisfactory anti-glioma effect via induction of cell apoptosis and cell growth inhibition in vitro. Furthermore, for subcutaneous tumor-bearing mice, treatment with the DMP–Gli 1 si complex significantly inhibited tumor growth by inhibiting Gli 1 protein expression, promoting apoptosis, and reducing proliferation.
Conclusion: The complex of Gli 1 siRNA and DMP may potentially play an important role as a new drug in the clinical treatment of gliomas.
Keywords: glioma, gene therapy, Gli 1, MPEG-PLA, DOTAP