高分子脂质体多功能纳米探针的基础研究

Recently, MR- fluorescence dual-modal imaging has attracted intense attention benefitting from the marrage of advantages in clinical diagnosis. However, the previous reported MRI-fluorescence dual-modal probes suffer from huge size, unstable structure, uncontrollability and complicated fabrication steps. As a result, it's hard to endow the dual-modal probes with targeting and other additional functions. Furthermore, the conventional near infrared quantum dots (NIR QDs) involved in dual-modal probes can't be used as MRI contrast agent and are also subjected with poor cytotoxicity. Inspired by the above issues, we design a new kind of multifunctional nanoprobe by assembling developed PCL-BSA based polymeric liposome with non-cadmium NIR bimodal QDs, targeting agent (folate), PEG chain and antitumor drug (doxorubicine), achieving MR-fluorescence imaging, tumor targeting, long circulation in body and drug controlled release perfectly. Based on the breast cancer model, the actual efficacy of MPL nanoplatform was extensively studied by toxicity test in vitro and in vivo, imaging detection in MRI- fluorescent image dual-mode, antineoplaston, all of which provide important evidence for early specific diagnosis of tumor and integration of diagnosis and treatment.

目前，MRI和荧光成像技术在肿瘤影像诊断中具有明显的互补优势，已引起国内外广泛关注。但已有的MRI-荧光双模态探针多存在粒径大、结构不稳定、可控性差、制备工艺复杂、不易实现特异性检测和多功能化等缺陷，并且制备双模态探针所用的量子点不能同时满足MRI造影、近红外荧光成像和生物安全性好的要求。针对上述问题，本课题拟以基于BSA-PCL键合体的新型高分子脂质体为载体，以自主研发的非镉近红外荧光和MRI双模态量子点（GdZnCuInS/ZnS）为造影剂，同时将肿瘤靶向制剂（叶酸）、体内长循环特性物质（PEG）和抗癌药物（阿霉素）等组分进行多功能组装，构建出集肿瘤靶向、体内长循环和药物缓控释治疗功能于一体的新型多功能MRI-荧光双模态纳米探针。并以乳腺癌为肿瘤模型，通过一系列的体内外实验，验证该多功能纳米探针的实际功效，为最大程度地实现肿瘤的早期特异性诊断和诊疗一体化提供重要的科学依据。

目前，MRI和荧光成像技术在肿瘤影像诊断中具有明显的互补优势，已引起国内外广泛关注。但已有的MRI-荧光双模态探针多存在粒径大、结构不稳定、可控性差、制备工艺复杂、不易实现特异性检测和多功能化等缺陷，并且制备双模态探针所用的量子点不能同时满足MRI造影、近红外荧光成像和生物安全性好的要求。针对上述问题，本课题以基于BSA-PCL键合体的新型高分子脂质体为载体，以自主研发的非镉近红外荧光和MRI双模态量子点（GdZnCuInS/ZnS）为造影剂，同时将肿瘤靶向制剂（叶酸）、体内长循环特性物质（PEG）和抗癌药物（阿霉素）等组分进行多功能组装，构建出集肿瘤靶向、体内长循环和药物缓控释治疗功能于一体的新型多功能MRI-荧光双模态纳米探针。经过四年的体外细胞实验及体内动物实验验证，我们成功构建了集肿瘤靶向、体内长循环和药物缓控释治疗功能于一体的新型多功能MRI-荧光双模态纳米探针，这一双模态纳米探针在诊疗一体化的应用过程中具有显著优势。同时取得了一系列成果，在本课题的支持下，以第一作者和通讯作者在国际顶级材料期刊如Advanced Materials, Advanced Healthcare Materials，ACS nano，ACS Applied Materials & interfaces等发表SCI论文共46篇（IF均>3），其中一区论文31篇。申请中国发明专利8项，其中授权5项。在本项目实施过程中，共培养硕士及博士研究生 21 名，超额完成了项目申请书的各项指标。本项目的实施为拓宽纳米探针的构建思路，解决MRI-荧光双模态探针的缺陷，研制新一代MRI-荧光双模态探针提供重要科学依据。