乳腺癌裸眼可视蓝色纳米靶向造影剂研究

People have been trying to improve outcomes in the diagnosis and treatment of breast cancer over the past decades. On the basis of our previous experience obtained from fabrication processes of tumor-targeted, intensely blue-colored NP agents for brain tumor-specific visible color contrast and methylene blue covalently loaded polyacrylamide nanoparticles for enhanced breast tumor-targeted photodynamic therapy, we propose the synthesis of blue iodinated targeted, multifunctional nanoparticles designed to improve the survival rate of breast cancer patients by increasing surgical efficiency. By optically imaging tumor margins, targeted multifunctional nanoparticles will enable maximal surgical resection, while minimizing damage to healthy adjacent tissue. In addition, the multifunctional nanoparticles conjugated by folate-PEG/CLT1-PEG will consist of a biodegradable polyacrylamide shell containing blue delineation dye and contrast agent. The iodinated blue tracers will exhibit good biocompatibility, water-solubility, and long residence time in the blood pool. Specifically, our goal is to synthesize dye-labeled iodinated nanoparticles that can be administered intravenously and selectively targeted to breast tumor cells MDA-MB-231. The iodinated nanoparticles will delineate neoplasm and healthy tissue, and increase contrast in CT images to improve early diagnosis of breast cancer. The interdisciplinary research proposal will offer new ideas and novel approaches for diagnosis and treatment of breast cancer in China, especially in the western region.

几十年来，人们一直致力于改进乳腺癌诊断与手术治疗的效果。我们在成功合成脑肿瘤裸眼可视蓝色靶向纳米粒子、体外乳腺癌细胞靶向PDT纳米粒子的基础上，进一步研究多功能靶向蓝色碘造影纳米示踪剂。这种含碘造影剂的蓝色聚丙烯酰胺纳米示踪剂经叶酸/CLT1聚乙二醇靶向修饰后，具有生物相容性好和水溶性好的特性,在血液中有较长的循环时间，能靶向导入裸鼠乳腺癌细胞MDA-MB-231，增强CT影像效果，并使乳腺瘤及淋巴结染成蓝色，在正常光线条件下，裸眼可视。该项跨学科研究，将给我国，特别是西部地区肿瘤的诊断与治疗带来新思路和新途径。

几十年来，人们一直致力于改进乳腺癌诊断与手术治疗的效果。我们在成功合成脑肿瘤裸眼可视蓝色靶向纳米粒子、乳腺癌细胞靶向PDT 纳米粒子的基础上，进一步研究多功能靶向蓝色纳米示踪剂。本课题用FDA或CFDA批准的磷脂、白蛋白、生物交联剂等生物材料、靶向多肽和人体必需元素为配位中心，一锅法自组装成纳米靶向生物膜配质体(简称配质体)。重点进行配质体稳定性研究，结构表征，光热转化规律研究，肿瘤细胞靶向实验研究。结果表明，这种蓝色的纳米配合脂质体示踪剂，不含胆固醇，平均粒子直径小于100 nm，具有生物相容性好和水溶性好的特性。在血液中有较长的循环时间，能靶向导入裸鼠乳腺癌细胞MDA-MB-231，将乳腺瘤染成蓝色，同时显示出磁共振影像增强效果。新的研究表明，在近红外光激发下，配质体可对肿瘤产生高效的光热、光动力协同治疗效果,可能克服肿瘤细胞对化疗的耐药性。该项跨学科研究，将给我国肿瘤的诊断与治疗带来新思路和新途径。