發(fā)布時(shí)間：2018-05-13 15:34

  本文選題：光動(dòng)力療法 + 吡咯并吡咯二酮�。� 參考：《南京郵電大學(xué)》2017年碩士論文

【摘要】：理論計(jì)算發(fā)現(xiàn),減少光敏劑單重態(tài)和三重態(tài)能級(jí)間的能級(jí)差(△EST)可大大促進(jìn)系間竄越(ISC)的速率。通過(guò)增加系間竄越的速率可增強(qiáng)光敏劑產(chǎn)生單線態(tài)氧的能力,進(jìn)而增強(qiáng)其抗腫瘤性能�；诖�,本文設(shè)計(jì)并合成了兩種吡咯并吡咯二酮(DPP)衍生物——苯基取代型吡咯并吡咯二酮(PDPP)和噻吩取代型吡咯并吡咯二酮(TDPP)。通過(guò)理論計(jì)算和實(shí)驗(yàn)研究發(fā)現(xiàn),TDPP比PDPP擁有更低能極差(△EST),具有更高的產(chǎn)生單線態(tài)氧的效率。隨后,我們對(duì)產(chǎn)生單線態(tài)氧效率更高的TDPP進(jìn)行化學(xué)修飾,通過(guò)共價(jià)鍵將聚乙二醇羧酸(mPEGCOOH)接到其側(cè)鏈得到TDPP-mPEG。進(jìn)一步實(shí)驗(yàn)發(fā)現(xiàn)TDPP-mPEG具有良好的水溶性、生理穩(wěn)定性以及光穩(wěn)定性。在此基礎(chǔ)上,我們將TDPP-mPEG與Hela細(xì)胞進(jìn)行培養(yǎng)后,通過(guò)熒光共聚焦顯微鏡可以看到TDPP-mPEG很容易被Hela細(xì)胞吞噬并分散在其細(xì)胞質(zhì)中。在特定波長(zhǎng)的光的照射下,Hela細(xì)胞的細(xì)胞核開始起泡、變圓,說(shuō)明TDPP-mPEG有良好的生物相容性,光照條件下,在細(xì)胞內(nèi)具有較好的抗腫瘤性能。我們還將TDPP-mPEG用于裸鼠體內(nèi),周期性的對(duì)比治療觀察發(fā)現(xiàn),光照情況下,TDPPmPEG可以顯著抑制腫瘤組織的生長(zhǎng),切片發(fā)現(xiàn)腫瘤組織已經(jīng)壞死,同時(shí),裸鼠體重在正常范圍內(nèi)變化,亦無(wú)其他不良反應(yīng),表明TDPP-mPEG對(duì)正常組織幾乎無(wú)損傷,且具有很好的光動(dòng)力治療效果。
[Abstract]:It is found by theoretical calculation that reducing the energy level difference (est) between the single and triplet states of Guang Min can greatly promote the rate of intersystem crossover. The ability of Guang Min agent to produce singlet oxygen can be enhanced by increasing the rate of interline crossover, and then its anti-tumor performance can be enhanced. Based on this, two derivatives, phenyl substituted pyrrolidine-pyrrolidinone (PDPPP) and thiophene substituted pyrrolidine-pyrrolidinone (TDPPN), have been designed and synthesized. Through theoretical calculation and experimental study, it is found that TDP has lower energy difference than PDPP, and has higher efficiency of producing singlet oxygen. Then we chemically modified the TDPP with higher singlet oxygen efficiency and connected the poly (ethylene glycol) carboxylic acid mPEGCOOH to the side chain to obtain TDPP-mPEG. Further experiments showed that TDPP-mPEG had good water solubility, physiological stability and photostability. On this basis, TDPP-mPEG and Hela cells were cultured and TDPP-mPEG was easily swallowed and dispersed in the cytoplasm of Hela cells by confocal fluorescence microscopy. The nuclei of Hela cells began to bubble and became round under the irradiation of specific wavelengths of light, which indicated that TDPP-mPEG had good biocompatibility and had better anti-tumor properties in the cells under light irradiation. We also used TDPP-mPEG in nude mice. Periodic comparative observation showed that TDPP mPEG could significantly inhibit the growth of tumor tissue, and the tumor tissue was necrotic, and the body weight of nude mice changed within normal range. There were no other adverse reactions, indicating that TDPP-mPEG had almost no damage to normal tissue and had good photodynamic therapy effect.
【學(xué)位授予單位】：南京郵電大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R914;R96

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 Wanqing Chen;Rongshou Zheng;Siwei Zhang;Ping Zhao;Hongmei Zeng;Xiaonong Zou;Jie He;;Annual report on status of cancer in China,2010[J];Chinese Journal of Cancer Research;2014年01期

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本文編號(hào)：1883785