本文選題：嵌段共聚物　切入點：點擊化學　出處：《中國科學技術大學》2017年碩士論文

【摘要】：近年來放射治療已經(jīng)成為目前腫瘤治療的主要手段之一,放射治療的效果顯著,據(jù)估計,有接近70%的癌癥患者愿意選擇接受放射治療來治療癌癥。目前,腫瘤放射治療領域的主要難題是如何應對乏氧腫瘤細胞的輻射抗性。由于高能的射線在輻照腫瘤的同時也會對正常組織有所影響,可能造成正常組織的嚴重損傷,因此不可能通過持續(xù)提高輻射劑量來殺死缺氧的腫瘤細胞。研究發(fā)現(xiàn)使用合適的放療增敏劑可以有效的提高對惡性腫瘤的放療效果,同時還能顯著的降低放療所需的輻射劑量,進而避免了對正常組織的損傷。本文主要研究了一種新型的兩親性嵌段聚合物放療增敏劑。與小分子放療增敏劑相比,不僅具有更高的增敏增強比,而且更穩(wěn)定,還能有效的富集在腫瘤部位從而顯著的提高放射治療的效果。這種聚合物放療增敏劑可以通過簡單高效的化學反應來合成,進而通過在水中自組裝制備。為了進一步研究了聚合物膠束的放療增敏效果,本文還分別在細胞層面和小鼠腫瘤模型層面上對聚合物膠束的放療增敏效果進行了評估。本論文的研究內(nèi)容以及主要結論如下:1、本文首先合成和制備了聚合物膠束。先將谷氨酸的一端羧基與丙炔醇反應修飾上炔基,又通過使用單端氨基聚乙二醇單甲醚作為引發(fā)劑,引發(fā)了谷氨酸丙炔酯的開環(huán)聚合反應,并得到了聚乙二醇-b-聚谷氨酸丙炔酯。通過一系列有機化學反應將甲硝唑末端的羥基轉(zhuǎn)變成了疊氮基團。最后使用點擊化學將兩種分子結合在一起,并最后終得到了單分散性的聚乙二醇-b-(聚谷氨酸-g-甲硝唑)。兩個嵌段的聚合度分別為113和60。將其溶于少量乙腈并加入水中,濃縮有機溶劑后可以得到聚合物膠束納米粒子。聚合物膠束粒徑約為60 nm,并具有很好的穩(wěn)定性。2、其次,為了從細胞層次上研究聚合物膠束的生物相容性和放療增敏性能,本文將聚合物膠束直接作用于細胞,并使用X射線進行放射治療。研究結果發(fā)現(xiàn),聚合物膠束在被細胞攝取后并未產(chǎn)生明顯的毒性;在接受X射線照射處理過后,乏氧的細胞的存活率大幅降低,并且表現(xiàn)出比小分子放療增敏劑更加優(yōu)異的增敏效果。3、最后通過建立小鼠腫瘤模型研究了聚合物膠束在生物體內(nèi)的分布以及配合放射治療的抑瘤效果。結果表明聚合物膠束能夠在短時間內(nèi)富集到腫瘤部位并且穩(wěn)定的存在;配合放射治療后能夠表現(xiàn)出顯著的抑瘤效果并且對正常器官組織不會造成任何損傷。
[Abstract]:In recent years, radiation therapy has become one of the main means of current cancer treatment, radiation treatment effect is remarkable, it is estimated that nearly 70% of the cancer patients are willing to choose to accept radiation therapy to treat cancer. At present, the main problems of tumor radiotherapy field is how to deal with the radiation resistance of hypoxic tumor cells. At the same time due to high-energy radiation the tumors were also affected the normal tissue, may cause serious damage to normal tissue, it is not possible through continuous improvement of radiation dose to kill the tumor cells. The study found that hypoxia can effectively improve the efficacy of radiotherapy for malignant tumor using suitable radiation sensitizer, and can significantly reduce the radiation dose of radiotherapy need, and avoid the damage to normal tissue. This paper mainly studies a new type of amphiphilic block copolymer two radiosensitizer and small. Sub radiosensitizer compared, not only has the higher sensitizing enhancement ratio, and more stable, but also can effectively improve the radiation to significantly enriched in the tumor therapy. This polymer radiosensitizer can be synthesized by chemical reaction is simple and efficient, and through self assembling in water for preparation. Radiotherapy is further studied polymer micelle sensitization effect, this paper at the level of cell level and tumor model mice on radiotherapy on polymer micelle sensitization effect was evaluated. The research contents of this thesis and the main conclusions are as follows: 1. Preparation of polymeric micelles firstly, synthesis and system. The first end carboxyl and propargyl the reaction of alcohol modified glutamate alkynyl, and through the use of a single amine terminated polyethylene glycol monomethyl ether as the initiator, led to the ring opening polymerization of glutamic acid propargyl ester, and poly ethylene glycol -b was obtained Polyglutamic acid propargyl ester. Through a series of organic chemical reaction will change at the end of the metronidazole hydroxyl azide groups. Finally using click chemistry two molecules together, and finally get the monodisperse polyethylene glycol -b- (poly glutamic acid -g- metronidazole). Two block polymerization degree respectively. 113 and 60. will be dissolved in a small amount of acetonitrile and adding water, concentration of organic solvent can be obtained after polymer micelle polymer micelle nanoparticles. The particle size is about 60 nm, and has very good stability of.2. Secondly, in order to study the polymeric micelles from the level of cell biocompatibility and radiation sensitizing properties, the polymer micelle a direct effect on the cell, and radiation therapy using X ray. The results of the study showed that the polymer micelles did not produce significant toxicity in cellular uptake; in an X ray irradiated after hypoxia The survival rate of cells significantly reduced, and showed than small molecule radiosensitizer more excellent sensitizing effect of.3, the distribution model of micelles was studied in vivo in mice tumor and radiotherapy combined with the inhibitory effect. The results show that the polymer micelles can in a short period of time to the tumor site and enrichment there were stable; combined with radiotherapy can show significant antitumor effect and no damage to normal tissues.

【學位授予單位】：中國科學技術大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R943;O631

【參考文獻】

相關期刊論文 前1條

1 閆宇邱,孫偉建,周平坤;放射增敏劑的作用機制及臨床研究進展[J];中華放射醫(yī)學與防護雜志;2004年03期

，

本文編號：1673348