基于金纳米颗粒的诊治结合靶向探针研究

发布时间：2018-04-25 20:30

本文选题：金纳米颗粒 + 诊治结合　；参考：《上海交通大学》2015年硕士论文

【摘要】：在肿瘤治疗技术中,放疗是极为重要的治疗手段。约有70%的肿瘤患者在疾病的某一阶段需要接受放射治疗,因此提高放射治疗效果非常重要。放射性增敏剂是临床上常用的提高放疗效果的方法。然而,传统的放射增敏剂如铂类、硝基咪唑类、紫衫类等药物,存在毒副作用大、对肿瘤细胞的选择性不强、难以在肿瘤内维持有效药效浓度等缺点,所以急需一种能够有效靶向肿瘤组织、毒副作用小、靶部位增敏治疗效果好并且能够减小周围组织损伤的放射增敏剂。金纳米颗粒作为高原子序数材料,生物相容性良好,能够进行放射性增敏治疗。同时,核素标记后还可以用于核医学成像,实现治疗的动态监控。但何种尺寸金纳米颗粒的体内行为最优,在靶部位能够富集最多,成像、治疗效果最好,仍是一个未解决的难题。因此,本研究在制备不同尺寸金纳米颗粒的基础上,对其进行核素锝-99m(99mTc)的标记、钆(III)标记和靶向肿瘤新生血管小肽(RGD)的修饰,评估不同尺寸金纳米颗粒放射性增敏治疗疗效。主要的研究内容包括:靶向肿瘤新生血管不同粒径金纳米探针的构建;探针细胞特异性及体内肿瘤靶向行为研究;靶向探针肿瘤放射性增敏疗效评估;I-125核素标记金纳米探针的制备及内放疗疗效评估。主要结果和结论:(一)成功的制备出了30nm、50nm、80nm的由核素锝-99m、钆(III)标记和RGD小肽偶联的靶向肿瘤新生血管金纳米(RGD@AuNP)靶向探针。这三种粒径的金纳米探针稳定性良好,且均具有良好体内生物学行为和肿瘤靶向性,能够特异靶向αvβ3受体,进行肿瘤放射性增敏治疗、SPECT/CT和MRI成像。其中30nm探针的成像效果与治疗效果最佳,有极大潜力成为用于肿瘤早期诊断与治疗的新型探针。(二)成功制备了30nm、由核素I-125的标记和RGD小肽偶联的靶向肿瘤新生血管金纳米靶向探针(125I-RGD@AuNP),该探针能够特异在肿瘤内部聚集,实现肿瘤内放疗和放射性增敏协同治疗。
[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 伪 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.
【学位授予单位】：上海交通大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R730.5;TB383.1

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