基于Ag2S近红外量子点的活体肿瘤新生血管可视化诊疗研究

Tumor angiogenesis is the basis of tumor growth, invasion and metastasis.Intratumoral microvessel density (MVD) is the gold standard for assessment of tumor angiogenesis and is an important biological index of the proliferative activity, invasiveness and the degree of malignancy of cancers. How to realize in situ real-time high resolution visualization of MVD is a great challenge in tumor clinical research area. Fluorescent imaging in the second near-infrared window (NIR-II 1000-1400 nm) can offer deep tissue penetration and high spatial resolution. Here, we will prepare highly photoluminescent and decently biocompatible NIR-II Ag2S quantum dots (QDs). Through surface functionalization of the QDs, linking high-affinity antibodies for targeting tumor vessels and anti-angiogenic drugs, we build a near-infrared quantum dot-based targeted drug delivery system for visual diagnosis and therapy of tumor angiogenesis. The research results will provide new approach which is based on in vivo fluorescent imaging technique for diagnose, therapy and drug evaluation of tumor angiogenesis, and further expand the applications of the near-infrared QDs in biomedical research.

肿瘤血管生成是肿瘤生长、侵袭及转移的基础。肿瘤微血管密度(microvessel density, MVD)是评估肿瘤血管生成的金标准，是反映肿瘤增殖能力、侵袭性及恶性度的重要生物学指标。如何实现原位实时高清观察MVD是目前肿瘤临床研究领域面临的一个焦点问题。近红外二区(NIR-II 1000-1400 nm)荧光成像具有高的组织穿透深度、高的空间分辨率等优点。本项目将研制具有高量子效率和高生物相容性的近红外二区Ag2S量子点，通过对其表面功能化，连接肿瘤血管特异性抗体分子及抗肿瘤血管生成药物，构建高效Ag2S近红外量子点靶向载药系统，运用于活体肿瘤新生血管的可视化诊疗研究。本项目的研究成果将有助于建立基于活体荧光成像的肿瘤血管生成诊断、治疗及药物评估的新方法，进一步拓展近红外量子点在生物医学领域的应用。

肿瘤血管生成是实体瘤典型特征之一，为肿瘤的生长、侵袭及转移提供基础，同时也为其治疗提供了新的靶点和途径。本课题的研究目标是构建一种基于Ag2S近红外量子点的肿瘤血管靶向纳米药物递送系统，实现高效的药物肿瘤靶向输送，并且借助近红外二区荧光影像高组织穿透、高空间分辨率特性实现治疗过程的实时可视化。按照预定计划，实现了高量子产率，粒径2.4-10 nm、近红外波长900-1200 nm精细调节的Ag2S近红外量子点的可控制备。作为纳米材料生物应用的关键步骤，分别采用化学合成分子及生物大分子两种策略进行Ag2S近红外量子点的表面功能化修饰，实现了好的生物相容性及体内代谢动力学特性。基于上述优化策略，我们设计、制备得到靶向肿瘤血管的Ag2S近红外量子点纳米药物递送系统。通过建立肿瘤动物模型，证实了该肿瘤血管靶向策略具有更好的药物递送效率，借助近红外二窗成像技术，实现了对瘤体大小、血管形态及密度的实时可视化监测。本项目的研究成果将有助于建立一种通用的纳米药物肿瘤血管靶向递送策略，实现肿瘤诊断、治疗和预后评估的一体化。