恶性肿瘤靶向诊疗的上转换荧光多功能供氧纳米探针的研究

Effective treatment of cancer is still the hot issue and a great challenge in the field of cancer research. Tumor hypoxia would be a direct cause of multi-drug resistance and severely limit the chemotherapy and photodynamic therapy (PDT) efficiency. Conventional PDT suffers mainly from the inaccessibility of visible light to the deep-cancer. These problems together with the poor cancer targeting induced side effects and the ineffective efficiency of monotherapy would reduce the therapeutic effect of cancer. The project would take advantages of the convert near-infrared light excitation to visible light fluorescence of upconversion nanoparticles, hydrogen peroxide catalyzed by catalase to quickly generate oxygen and the high oxygen capacity of perfluorocarbon, and construct a class of multifunctional oxygen supply nanoprobes, which possess the properties of greater penetration depths, cancer targeting, oxygen self-sufficiency, combined therapy and therapeutic self-monitoring. The multifunctional oxygen supply nanoprobes will be used to the upconversion fluorescence imaging diagnosis, combination of chemotherapy with PDT, and therapeutic self-monitoring of hypoxic tumor. This project is expected to develop novel multifunctional nano-theranostics for overcoming tumor hypoxia induced poor therapeutic efficiency, and for highly effective theranostics and therapeutic self-monitoring of hypoxic tumor, which has a potent value for clinical applications.

实现癌症的有效治疗是全世界癌症研究领域的热点问题和一大挑战。肿瘤乏氧限制光动力学治疗效果和促进肿瘤多药耐药性产生降低化疗效果、可见光组织穿透力不足影响光动力学治疗效果、非靶向治疗引起毒副作用以及单一疗法疗效不够理想，都会降低癌症治疗效果。本项目拟利用上转换纳米颗粒的近红外光激发特性、过氧化氢酶催化过氧化氢产生氧气和全氟化碳的高携氧能力，构建一类具有组织穿透力强、肿瘤靶向性、氧气自足、联合治疗以及疗效监测的多功能供氧纳米探针，用于乏氧肿瘤的上转换荧光成像诊断、光动力学-化学联合治疗以及疗效监测。本项目的研究成果有望开发新型的多功能纳米诊疗探针，解决肿瘤乏氧引起的疗效降低问题，用于乏氧肿瘤高效诊疗和疗效及时监测，具有潜在的临床应用价值。

开发新型的多功能纳米诊疗探针，实现癌症的有效治疗具有重要意义。本项目构建了同时具有组织穿透力强、肿瘤靶向性、联合治疗的多功能上转换纳米探针，用于肿瘤的上转换荧光成像诊断、光动力学-光热联合治疗研究。此外，生物标志物的检测与分析对临床疾病早期诊断意义重大。本项目研究了系列纳米材料的制备、功能化及相关性能，并结合核酸信号转换与放大技术，以酶活性、金属离子为研究对象，建立了一系列高灵敏度、高特异性的生物分析方法，为临床疾病早期诊断的研究提供了重要理论与技术参考。相关研究成果已经形成Analytical Chemistry，Biosensors and Bioelectronics，Sensors and Actuators B: Chemical，Microchimica Acta，Talanta等生物传感领域重要国际学术论文10篇，其影响因子均大于4.0，均标注本项目资助。申请国家发明专利3项。同时，项目组协助培养博士研究生2名，硕士研究生4名。基本完成了既定目标和任务。