4.3 Article

Cationic micelle-based siRNA delivery for efficient colon cancer gene therapy

Journal

NANOSCALE RESEARCH LETTERS
Volume 14, Issue -, Pages -

Publisher

SPRINGER
DOI: 10.1186/s11671-019-2985-z

Keywords

Non-viral vector; Gene therapy; Gene delivery; RNAi; siRNA; C26 colon cancer

Funding

  1. National Natural Science Foundation [NSFC81502677]
  2. Key Technologies R&D program of Sichuan Province [2015FZ0040]
  3. Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital Foundation [2016QN08]
  4. Sichuan Provincial People's Hospital Foundation [2016QN03]
  5. Chengdu science and technology development project [2016-HM01-00438-SF]
  6. National Key Specialty Construction Project of Clinical Pharmacy [30305030698]

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Small interfering RNA (siRNA)-based gene therapy has provided an alternative strategy for cancer therapy. One of the key components within gene therapy process is the delivery system. As a novel non-viral gene vector, DMP, prepared by modifying mPEG-PCL micelle with cationic DOTAP lipid, has been prepared and successfully applied in plasmid DNA-based colon cancer gene therapy study. However, its potential in siRNA delivery is unknown. In this study, the preparation process of DMP was optimized and the anti-cancer efficacies of the DMP/siMcl1 and DMP/siBcl-xl complexes were studied on a mouse colon cancer model. Our results demonstrated that DMP cationic micelle-delivered siRNAs could effectively inhibit the growth of C26 colon cancer cells in vitro. Meanwhile, intratumoral administration of DMP/siMcl1 and DMP/siBcl-xl complexes obviously suppressed subcutaneous tumor model in vivo. These results suggest the DMP/siRNA complex to be a potential candidate for cancer gene therapy.

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