PSCA核酸适体靶向纳米探针可视化前列腺癌转移灶的研究

核磁共振技术（MRI）是广泛应用于临床评估前列腺癌转移的方法，但是由于缺乏特异性的MRI探针，敏感性和特异性均不高。我们前期的研究发现，以前列腺干细胞抗原(PSCA)作为靶点，以超顺磁性四氧化三铁(SPIO)作为MRI造影剂，在体外可成功使转移性前列腺癌细胞特异性显像。本课题在前期的研究基础上继续深入，拟研发可能应用于临床的靶向纳米探针，以PSCA特异性的DNA核酸适体作为靶向配体，利用聚乙二醇(PEG)作为转运体转运SPIO，采取可控的合成体系构建前列腺癌转移灶特异性的靶向纳米探针，并且从医学的角度，以应用于体内为目标，对整个纳米体系进行优化选择，从体外3-D细胞培养模型向体内过渡，使原位前列腺癌转移动物模型特异性、靶向性显像，探讨前列腺癌转移灶特异性的靶向纳米探针成功应用于体内的关键因素，提高前列腺转移灶的诊断水平，为进一步的临床实验打下基础。

Magnetic resonance imaging(MRI) is an appealing imaging modality that is used to evaluate the metastasis of the prostate cancer in clinical practice. However, due to the paucity of the specific MRI imaging probe, the sensitivity and specificity of diagnosis is limited. In our initial, proof-of-principle study, we have recently demonstrated that an MRI imaging probe, consisting of superparamagnetic iron oxide nanoparticles (SPIO) for MRI imaging and a single-stranded prostate stem cell antigen (PSCA) antibody for targeting moiety, could generate the negative contrast enhancement in the metastatic cells of prostate cancer in vitro. In the context of our earlier studies ,for translation from the laboratory to clinical use, we plan to elaborate a poly(ethylene glycol) (PEG)-coated and aptamer-conjugated SPIO nanoprobe that is capable of specifically targeting the metastasis of the prostate cancer via the surface-bound DNA aptamer of PSCA using a pragmatic and flexible strategy. After the optimization of the targeted nanoprobe, we will investigate the specific and targeted contrast enhancement of nanoprobes in 3-D cell aggregates in vitro and in orthotopic metastatic prostate cancer model in vivo and explore the determined factors of successful application of SPIO-based nanoprobe in metastasis of prostate cancer in vivo. We believe that our study has potential for providing the data for improve the diagnosis of the metastasis of the prostate cancer in clinical use.