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  • 學位論文

發展具DNA切割能力之新型奈米材料與鉑化合物

Novel DNA-nicking Nanomaterials and Platinum Complexes

指導教授 : 胡紀如
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摘要


於本篇論文中,本人將光引導去氧核醣核酸切割試劑與第三股螺旋寡核苷酸鏈及奈米粒子相結合,形成新型具有專一性切割去氧核醣核酸能力之奈米材料。另外,本人也合成新型奈米材料作為新穎之去氧核醣核酸切割試劑。除此之外,本人也製備一系列鉑錯化物衍生物做為新型抗癌藥物之研究。 本論文第一部分,本人將光引導去氧核醣核酸切割試劑藉由第三股螺旋寡核苷酸鏈當架橋,與金奈米粒子相結合,形成新型具有專一性切割去氧核醣核酸能力之奈米材料。 第二部分中,本人成功製造出四種新型奈米材料,各為二種新型具鐵磁性之光引導去氧核醣核酸切割奈米粒子,其平均直徑為6.2奈米,可由核磁共振造影技術追蹤此奈米粒子,另二種為新型光引導去氧核醣核酸切割之金奈米粒子。此四種新型奈米材料皆可利用紫外光作為釋放有機分子的板機。 第三部分中,本人設計並合成出具有DNA切割能力及作為抗癌先導藥物之新型有機白金化合物。此外,本人亦利用紫外光照射白金化合物之方式,探討對X174 RFI去氧核醣核酸之切割效果。這些新型化合物具有抑制癌細胞之能力。其中活性最佳之有機白金化合物的抑制半數生長濃度為1.3 M。 In this thesis, I developed a novel DNA-nicking material for sequence specific cleavage of double-stranded DNA. New nanomaterials were synthesized as a novel DNA cleaving agent. Furthermore, I synthesized the platinum complex derivatives to act as a new class of anti-cancer agents. In part 1 of this thesis, a photo-induced DNA-cleaving nanowarhead was developed for accuracy cleavage of DNA at specific target sequences. The nanomaterial is comprised of nanoparticle-core and a monolayer of hydrazone-modified triplex-forming oligonucleotide (TFO), which recognize and nick the targeted DNA duplex. The attached hydrazone “warhead” specifically cleaves the targeted DNA at a specific nucleotide pair. This nanomaterial thus may be a new pathway for the development of in vitro gene-manipulation tools and in vivo gene-therapy strategies. In part 2, I reported our success in the development of four types of organic molecules-conjugated nanoparticles. Two phenylnitrone-conjugated nanoparticles and two phenylhydroxylamine-conjugated nanoparticles were synthesized by use of Fe3O4 and Au as the cores. The UV light could be as a trigger to release organic molecules. This nanomaterial improved the cleaving potency. In part 3, I used novel sulfoplatin as lead compound to develop a series of novel platinum anti-cancer drugs. Various new platinum complexes were synthesized, which exhibited ability for single-strand scission of DNA upon UV irradiation. The platinum complex can nick DNA at the concentrations as low as 6.7 M. In vitro growth inhibitory effect of those organoplatinum complexes were evaluated in human cancer cells (OECM1) by the MTT assay. The platinum complex inhibited cancer growth at an IC50 of as low as 1.3 M.

並列摘要


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參考文獻


5. Huang, E. H.; Hynes, M. J.; Zhang, T.; Ginestier, C.; Dontu, G.; Appelman, H.; Fields, J. Z.; Wicha, M. S.; Boman, B. M. Cancer Res. 2009, 69, 3382–3389.
33. Longley, D. B.; Harkin, D. P.; Johnston, P. G. Nat. Rev. Cancer 2003, 3, 330–338.
8. Sadler, P. J. ChemBioChem 2009, 10, 73–74.
11. Puckett, C. A.; Barton, J. K. Biochemistry 2008, 47, 11711–11716.
12. Puckett, C. A.; Barton, J. K. J. Am. Chem. Soc. 2007, 129, 46–47.

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