Title page for etd-0723117-132050


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URN etd-0723117-132050
Author Hao-Han Pang
Author's Email Address No Public.
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Department Institute of Medical Science and Technology
Year 2016
Semester 2
Degree Master
Type of Document
Language zh-TW.Big5 Chinese
Title Using Multifunctional Qβ Virus-Like Particles for RNAi and Reducing Temozolomide Resistance in Brain Tumor
Date of Defense 2017-07-26
Page Count 100
Keyword
  • drug resistance
  • RNAi
  • VLPs
  • Virus-like particles
  • Brain Tumor
  • Temozolomide
  • Abstract Introducion
    Brain tumour is one of the most lethal cancers due to difficulties of delivering therapeutic agents across blood-brain barrier (BBB) and serious side effect. Here, we describe a virus-like particles (VLPs) platform as multifunctional nanocarriers to deliver RNA molecules and fluorescence proteins for RNA interference and imaging tracking.
    Methods
    We have designed an RNA scaffold and co-expressed with Qβ coat protein and green fluorescent protein (GFP) or mCherry protein simultaneously through a two-plasmid system. Coat proteins and cargos will be produced and self assembled in E. coli. The TAT and ApoE peptide, were then incorporated to the exterior surface of VLPs via a linker (sulfo-SMCC) to enhance cell uptake and promote BBB penetration.
    Results
    The functional VLPs have been assessed by cell examination. VLPs do not show cytotoxicity and can be internalized insides cells. VLPs containing RNA molecules and GFP modulate gene expression and serve as fluorescent trackers within U87 cells. VLPs containing RNAi scaffold for c-MET silencing and GFP (c-MET@t-gVLPs) successfully down regulated the c-MET protein expression level of U87 cell. c-MET@t-gVLPs treated cells also showed lower Temozolomide (TMZ) drug resistance and limited cell migration.
    ApoE conjugated VLPs have the ability to cross the BBB in vivo. Current findings showed that our VLPs could be a good RNAi delivery plateform for gene down-regulation therapy.
    Conclusion
    We believe this multifunctional VLP platform has potential to overcome impediments as mentioned earlier and well suited for RNAi-based therapeutic tools for brain tumour therapy.
    Advisory Committee
  • Kuo-Chen Wei - chair
  • Chiao-Long Hsiao - co-chair
  • Hung-Wei Yang - advisor
  • Files
  • etd-0723117-132050.pdf
  • Indicate in-campus at 3 year and off-campus access at 5 year.
    Date of Submission 2017-08-28

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