本文選題：金納米顆粒 + 診治結(jié)合��； 參考：《上海交通大學》2015年碩士論文

【摘要】：在腫瘤治療技術(shù)中,放療是極為重要的治療手段。約有70%的腫瘤患者在疾病的某一階段需要接受放射治療,因此提高放射治療效果非常重要。放射性增敏劑是臨床上常用的提高放療效果的方法。然而,傳統(tǒng)的放射增敏劑如鉑類、硝基咪唑類、紫衫類等藥物,存在毒副作用大、對腫瘤細胞的選擇性不強、難以在腫瘤內(nèi)維持有效藥效濃度等缺點,所以急需一種能夠有效靶向腫瘤組織、毒副作用小、靶部位增敏治療效果好并且能夠減小周圍組織損傷的放射增敏劑。金納米顆粒作為高原子序數(shù)材料,生物相容性良好,能夠進行放射性增敏治療。同時,核素標記后還可以用于核醫(yī)學成像,實現(xiàn)治療的動態(tài)監(jiān)控。但何種尺寸金納米顆粒的體內(nèi)行為最優(yōu),在靶部位能夠富集最多,成像、治療效果最好,仍是一個未解決的難題。因此,本研究在制備不同尺寸金納米顆粒的基礎上,對其進行核素锝-99m(99mTc)的標記、釓(III)標記和靶向腫瘤新生血管小肽(RGD)的修飾,評估不同尺寸金納米顆粒放射性增敏治療療效。主要的研究內(nèi)容包括:靶向腫瘤新生血管不同粒徑金納米探針的構(gòu)建;探針細胞特異性及體內(nèi)腫瘤靶向行為研究;靶向探針腫瘤放射性增敏療效評估;I-125核素標記金納米探針的制備及內(nèi)放療療效評估。主要結(jié)果和結(jié)論:(一)成功的制備出了30nm、50nm、80nm的由核素锝-99m、釓(III)標記和RGD小肽偶聯(lián)的靶向腫瘤新生血管金納米(RGD@AuNP)靶向探針。這三種粒徑的金納米探針穩(wěn)定性良好,且均具有良好體內(nèi)生物學行為和腫瘤靶向性,能夠特異靶向αvβ3受體,進行腫瘤放射性增敏治療、SPECT/CT和MRI成像。其中30nm探針的成像效果與治療效果最佳,有極大潛力成為用于腫瘤早期診斷與治療的新型探針。(二)成功制備了30nm、由核素I-125的標記和RGD小肽偶聯(lián)的靶向腫瘤新生血管金納米靶向探針(125I-RGD@AuNP),該探針能夠特異在腫瘤內(nèi)部聚集,實現(xiàn)腫瘤內(nèi)放療和放射性增敏協(xié)同治療。
[Abstract]:In tumor therapy, radiotherapy is a very important treatment method. About 70% of cancer patients need radiotherapy at some stage of the disease, so it is very important to improve the effect of radiotherapy. Radiosensitizer is a commonly used method to improve the effect of radiotherapy. However, traditional radiosensitizers, such as platinum, nitroimidazole and purplish, have many disadvantages, such as large side effects, low selectivity to tumor cells, and difficulty in maintaining effective drug concentration in the tumor. So it is urgent to have a radiosensitizer which can target tumor tissue effectively, have less toxic and side effects, sensitize the target site and reduce the damage of surrounding tissues. As a high atomic number material, gold nanoparticles have good biocompatibility and can be used for radiosensitization therapy. At the same time, radionuclide labeling can also be used in nuclear medicine imaging to achieve dynamic monitoring of treatment. However, it is still an unsolved problem that what size gold nanoparticles have the best behavior in vivo, can enrich the most in the target site, imaging and treatment is the best. Therefore, on the basis of the preparation of gold nanoparticles of different sizes, the radiosensitization effects of different sizes of gold nanoparticles were evaluated by the labeling of technetium 99mTc, the labeling of gadolinium III and the modification of RGGD targeting tumor neovascularization peptides in order to evaluate the effect of radiosensitization of gold nanoparticles of different sizes on radiosensitization. The main research contents are as follows: the construction of gold nanoparticles with different particle sizes targeting tumor neovascularization, the study of cell specificity and tumor targeting behavior in vivo; Evaluation of radiosensitizing effect of targeted probe on tumor: preparation of I-125 radionuclide labeled gold nanoprobe and evaluation of the efficacy of internal radiotherapy. Main results and conclusions: (1) We successfully prepared a 30nmTc-50nmc-80nm labeled RGD-DB-AuNPNP-targeted probe coupled with a small peptide of RGD labeled with radionuclide technetium (Tc-99m, gadolinium). These three kinds of gold nanoparticles have good stability, good biological behavior in vivo and tumor targeting, and can specifically target 偽 v 尾 3 receptor for tumor radiosensitization therapy and SPECT / CT and MRI imaging. Among them, 30nm probe has the best imaging effect and therapeutic effect, and has great potential as a new probe for early diagnosis and treatment of tumor. (2) A 30nm ~ (-1) probe, which was labeled by radionuclide I-125 and coupled with a small peptide of RGD, was successfully prepared. The probe can specifically aggregate within the tumor and achieve the cooperative therapy of intra-tumor radiotherapy and radiosensitization.
【學位授予單位】：上海交通大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R730.5;TB383.1

【參考文獻】

相關期刊論文 前1條

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本文編號：1802845