基于硫化铋纳米体系的多模态分子影像探针及其肿瘤靶向诊疗

Nanoprobes have attracted intense attentions due to their strong imaging intensity, good target property and controlled pharmacokinetics. The development of new and efficient multimodal imaging probes is the key to the early imaging of tumor. Based on nanotechnology, nanoprobes have attracted intense attentions and showed good imaging effect because their strong imaging intensity, good target property and controlled pharmacokinetics. Photoacoustic (PA) imaging is a novel technique with no radiation, no damage and high resolution properties and has recieved great concern on tumor imaging. Among them, PA nanoprobes with good near infrared (NIR) absorption in the targeted tumor imaging attract more attention. Developing nanoprobes with good optical stability, strong NIR absorption, good targeting and biocompatibility have become a hot spot. In addition, the PA probes can be used as photothermal therapy (PTT) probes, which are also based on strong NIR absorption. Our project proposed to develop novel PA/CT/PTT multimodality nanoprobes based on Bi2S3 nanomaterials with native strong X-ray mass attenuation coefficients, good NIR light absorption, light stability and biocompatibility. The Bi2S3 nanomaterials are design and synthesized via adjusting the composition, size and their functional groups under different condition. The structure-optical property relationships are investigated. The Bi2S3 nanomaterials modified with target molecules which can target the tumor cell. Finally, the performances of the nanoprobes are evaluated through investigating the targeting imaging and photothermal therapy property to tumor cells and tumors in vivo. We hope this work will be beneficial to developing PA/CT/PTT multimodality nanoprobes with high performances.

发展新型有效的多模态分子影像对于肿瘤的早期诊断至关重要。光声成像技术是一种新兴的无创、无辐射、高分辨成像技术。但是光声成像的穿透深度仅限于几厘米，如果将CT成像深度深的特点与光声成像分辨率高的特点相结合，能极大的提高肿瘤早期诊断的精确性。另一方面，由于光声成像与光热治疗从原理上都是基于对光能量的吸收及光-热能量转化，将三种技术结合在一起, 可以实现光声/CT成像监测下的肿瘤光热治疗。本课题提出开发基于硫化铋纳米体系的多模靶向分子探针，充分利用其本身光吸收强、光稳定性好、生物毒性小以及具有较高的X射线衰减系数等特点，从调控硫化铋纳米材料的组成、大小和功能修饰基团等方面入手，研究其结构组成、粒径大小、表面化学性质与光声/CT成像以及光热治疗效果的关系；通过修饰靶向分子，研究纳米探针与其高效偶联方法；研究硫化铋多模纳米探针其对活体的肿瘤的靶向性以及其光声/CT /光热治疗效能。

多模态成像与光疗技术相结合将会有效地实现对癌症的早期诊断和提高治疗效率，而集多模态成像功能与高效光疗性能于一体的纳米诊疗剂是实现早期诊断和有效治疗的关键。本项目围绕多功能纳米探针的设计与应用角度出发，开展多功能纳米材料的合成及其生物传感和光学诊疗方面的研究工作。研制了一系列金属、半导体、无机/有机复合物等纳米材料；探讨了控制纳米粒子尺寸、形貌及其结构的方法，研究了不同条件下各种纳米材料的生长机理；通过与具有特异选择或识别功能的生物分子定向偶联，进行针对肿瘤靶点的靶向修饰；探讨了它们的化学性质、光电性质以及在生物传感及生物医学影像方面的性能，实现了从DNA/micro RNA、外泌体、细胞到动物肿瘤组织靶向检测和多模态光学诊疗。. 在项目资助下，开发出5种低毒高效、生物安全性高的多模态纳米诊疗探针，在Advanced Functional Materials、 Analytical Chemistry、 Theranostics、ACS Appl. Mater. Interfaces等国际著名期刊上发表文章16篇，申请和授权中国发明专利共10项，其中授权3项，参加国际、国内学术会议6次，并受邀做口头报告3次。在多模态纳米诊疗探针构建及其活体肿瘤的检测与治疗等方面获得了一些阶段性的成果。这些研究结果不仅有助于肿瘤的早期检测，而且为肿瘤组织的多模态诊疗提供了有用的平台。其在肿瘤的临床医学影像诊断和新型治疗中具有很大的应用潜力，对发现新的影像探针和抗癌药物方面具有潜在的应用价值。