聚酯光声探针的构建及对间充质干细胞的标记与示踪研究

Photoacoustic imaging (PAI) is an advanced non-invasive dual imaging modality. It has the advantages of high contrast and deep penetration depth, and can provide high-resolution and enhanced-contrast structural and functional images. It is important to construct novel PAI probes with appropriate materials and strategy to further enhance the imaging quality, label and track the reporters at a molecular and cellular level. Mesenchymal stem cells (MSCs) are adult stem cells with self-renewing and differentiation potentials. The differentiated and transplanted MSCs are able to significantly boost the renewing of cardiac muscle cells and improve the myocardial contractility, and thus MSCs are a major tool to study and therapy the myocardial infarction-related ischemic diseases. Therefore, it is of great value to utilize molecular probes associated with PAI for MSCs labeling and tracking to elucidate the mechanism of injured myocardium recovery. To this end, this project aims to develop biocompatible and stable polyacrylate-based PAI probes to label MSCs, track MSCs-medicated biological processes, real-time monitor the recovery of injured myocardium in vivo, and preliminarily investigate the therapy and mechanism against myocardial infarction. This will not only benefit the development of PAI probes and imaging technology, but also afford a new opportunity to solve the bottleneck of imaging-guided diagnostics and disease treatments.

光声成像是一种新型无损双模态分子影像技术，它结合了光学成像对比度高和声学成像穿透度深等优点，因此能够提供高分辨率和对比度的组织与功能影像。选择合适的材料与策略构建光声探针对于进一步提高成像质量、在分子与细胞水平上实现对报告基团的标记与示踪具有重要的研究价值。间充质干细胞是具有自我更新和分化潜能的成体干细胞，其分化、移植能显著促进心肌细胞再生、改善心肌收缩功能，目前已成为心肌梗死等缺血性疾病研究与治疗的主要手段。因此，结合分子探针、光声成像研究间充质干细胞的标记、示踪及修复受损心肌的机制具有重要意义。本课题旨在通过不同策略构建新型生物相容、体内稳定的聚酯探针并用于间充质干细胞的标记，结合光声成像活体示踪其参与的生物学过程、动态监测受损心肌的修复，为初步探究梗死心肌的治疗与机理提供实验依据。此项研究不仅有助于发展现有光声成像与探针体系，还将为解决分子影像辅助疾病治疗中的瓶颈问题提供新思路。

光声成像是一种新型无损双模态分子影像技术，它融合了光学成像高灵敏度和声学成像深组织穿透性的优点，使高分辨率与对比度的组织、功能影像成为可能。具有微纳尺度的复合生物材料具有粒径小、表面积大、生物相容性好、易于偶联特异性生物大分子等优点，选择合适的材料合成策略构建肿瘤靶向的光声探针对于在分子、细胞水平上实现病理发展的高灵敏度实时监测、长生命过程的直观影像学分析与功能物质的特异性递送具有重要的研究价值。本项目通过分子设计、绿色合成开发了一系列可用于光声成像的微纳分子探针，如高分子载气微泡、碳纳米点及聚酯纳米粒子等，通过表面偶联配体实现了对肿瘤细胞表面过表达的叶酸受体、整合素αvβ3受体的特异性靶向，在较低浓度（2.5 mg/L）下实现了高灵敏度、长示踪时间的光声成像，为在活体内实施间充质干细胞的标记示踪与干细胞移植评价促心肌细胞再生及改善提供了强大工具与崭新方案。同时，本课题还研究了微纳材料对阿霉素等模型药物的增药负载与超声触发的响应释药行为，并在乳腺癌接种的荷瘤裸鼠上验证了这一方案的可行性与有效性，从而为深入拓展光声探针的多样化生物医学应用、不断充实光声对疾病诊疗的科学作用奠定了丰富的实验基础。