多功能纳米酶比色探针用于乳腺癌循环肿瘤细胞快速分离和协同放大可视化检测的研究

The circulating tumor cell detection showed great potential for early cancer diagnosis, tumor evolution monitoring and prognostic prediction. However, a great challenge is to efficiently capture low abundant circulating tumor cells with high purity from blood samples for accurate and sensitive circulating tumor cell detection. We intend to construct a robust sensing platform for targeted recognition, separation and amplified colorimetric detection of breast cancer circulating tumor cells enabled by gold nanoclusters entrapped in magnetic mesoporous silica nanoparticles. So far, colorimetric detection of circulating tumor cells based on metal nanocluster nanozyme has not been reported yet. Combined with high loading efficiency and enzyme optimization functions of magnetic mesoporous silica nanoparticles, as well as enzymatic amplification capability of gold nanoclusters, the hybrid nanoplatform served as a synergistic amplified colorimetric sensor for efficient circulating tumor cell detection. Taking advantage of the intrinsic peroxidase-like activity of ferromagnetic nanoparticles, the detection sensitivity can be further improved. Optimization of the density and ratio of the targeting molecules can further reduce the impact of heterogeneity and increase the capture efficiency of circulating tumor cells, which may make this platform suitable for single cell detection. In addition, the colorimetric detection results can be directly visualized with naked eyes and do not require complex detection instruments. Therefore, it is expected to provide theoretical and experimental basis for the development of the convenient circulating tumor cell detection kit in the future.

循环肿瘤细胞检测在癌症早期诊断、疗效监测和预后评估等方面都具有重大的应用潜力。目前，高纯度捕获和高灵敏度检测低丰度循环肿瘤细胞仍是一个巨大挑战。本项目拟通过靶向分子修饰的介孔硅-磁性纳米粒子装载高催化活性的纳米酶金簇，实现乳腺癌循环肿瘤细胞的快速识别、分离和可视化比色检测。基于金属簇纳米酶比色体系实现循环肿瘤细胞检测还鲜有研究。结合金簇的酶催化放大效应，以及介孔硅对金簇的高负载效率和其酶活性的优化作用，可实现循环肿瘤细胞协同放大可视化检测。此外，铁磁纳米粒子的过氧化物酶活性可进一步提高检测灵敏度。项目拟通过同时引入多种靶向分子改善循环肿瘤细胞异质性导致检出率低的问题，以期提高捕获效率，有望实现单个循环肿瘤细胞的检测。此外，直观的肉眼可视化比色检测不需要复杂的检测仪器，有望为未来发展便捷可视化的循环肿瘤细胞检测试剂盒提供理论和实验依据。

癌症等疾病的早期诊断和治疗在提高患者治愈率和生存率，减轻患者痛苦和精神、经济负担等方面具有重要意义。纳米酶是具有类酶特性的纳米材料，由于稳定性高、制备方便、成本低、易功能化修饰等优点，在疾病诊疗方面具有重大的应用潜力。本项目基于纳米酶构建了一系列纳米复合材料体系，应用于癌症等疾病的诊断和治疗领域，为之后基于纳米酶的生物诊断和治疗提供了新思路和新方法。主要研究内容包括：1）构筑血清蛋白-金属纳米簇蛋白冠稳定的聚苯乙烯纳米颗粒用于乳腺癌细胞的双信号检测和特异性捕获；2）应用多功能纳米酶探针有效实现肝炎的诊断；3）构建多功能纳米酶复合体系应用于癌症疾病的有效治疗。共发表SCI收录论文31篇，申请发明专利3项。