新型miR21靶向肿瘤反义核素显像与治疗研究

miRNAs是调节基因表达的非编码RNA，与肿瘤发生及发展关系密切，为潜在的肿瘤标志物。开展肿瘤组织异常表达miRNAs的可视化及靶向治疗，有望为肿瘤的诊断和治疗开辟新途径。现有miRNAs显像采用报告基因，通过基因治疗进行显像，但病毒载体的不安全性使其难以推广；miRNAs靶向治疗采用与miRNAs互补的反义核酸，该法缺乏靶向性、难以进入肿瘤细胞，无法有效抑制肿瘤。本研究拟以反义核酸互补结合为理论依据，利用NGR靶向肿瘤新生血管及穿膜肽TAT介导细胞转入的作用，以肿瘤过度表达的miR21为靶点，合成肿瘤靶向性抗miR21反义肽核酸PNA。以99mTc标记新型反义探针对肿瘤进行显像，开展肿瘤诊断及疗效评价的研究；以177Lu标记，通过联合PNA对miRNA的抑制作用及核素的电离辐射效应，开展肿瘤治疗研究。最终建立miRNA靶向的核素反义显像与治疗新方法，为提高肿瘤诊断与治疗效果开辟新途径。

miRNAs, non-coding RNA which close related with tumorigenisis, could be new tumor biomarkers. Targeted miRNAs for tumor diagnose and therapy may explored a new way for tumor theranostic. Howerver,existed miRNA imaging depends on the reported gene through genetherapy, but its broadly use will be limited because of the dangours of virus in gene therapy. Target miRNA for therapy always adopt single modified antisense(antagmir), its disadvantages of lacking of tumor targeting and difficult in passing through cell membrane resulted uneffective inhibiting the tumor growth. To solve those critical problems in tumor imaging and therapy by target miRNA, this study will introduce the tumor angiogenesis target peptide NGR and the cell penetrating peptide TAT to antagmir to prepare a completely new peptide nuclide acid PNA target miR21 which is broadly over expressed in many solid tumors. By labeling the new probe with 99mTc, it will be used for imaging miR21 expressed in tumor for tumor diagnose and evaluation the therapy. By labeling the new probe with 177Lu, the tumor growth will be significantly inhibited by combing the PNA inhibit expression of miR21 and β particles from 177Lu which will completely destroy the cells. The utmost aim of this study will established a new method in tumor imaging and therapy, which will be open a new window for studies of both the miRNAs and tumors.