靶向降冰片烯共聚物在癌细胞荧光成像中的应用

Cancer, or malignant tumor, is one of the most serious threatens for human health and life. It is widely accepted that successful cure of most cancers primarily relies on early detection and timely treatment. Clinical diagnosis for early-stage cancer mainly depends on the definition of specific products of metabolism or tissue slides, which remains at the macrofunctional and anatomical level and limited to many factors. Molecular imaging (such as fluorescence imaging, etc.) techniques are now indispensable tools in modern diagnostics, because they are highly specific, enable visualization of some disease processes and provide biological information at the molecular level in living systems. To support the unmet needs for molecular imaging, there has been considerable interest in investigating highly specific targeted and labelled imaging probes. Therefore, this proposal intends to design and synthesize functionalized norbornenes with capabilties of water-solubility, targeting, fluorescent labelling through chemical modification, prepare polymeric imaging probes directly via a random ring-opening metathesis polymerization (ROMP) using Grubbs' catalyst as an initiator, and realize optical fluorescence imaging for diverse tumor cells or specific organelles on the cellular level through targeting function groups and chrmophores tethered copolymers under varied wavelength and channels. Our main goal is to develop a series of novel, practicable, multi-functional, biocompatible copolymers and materials in the field of cancer diagnosis and therapy.

癌症是当今威胁人类健康和生命最严重的疾病之一，早期发现并及时治疗是战胜癌症的首要问题。传统的癌症 检测方式受到体内代谢产物浓度太低的限制，很多特异性指标检测精度不高；基于微观细胞层面的荧光成像技术，能够实现对癌变组织或细胞的可视化灵敏检测，有可能大大提高早期癌症特异性指标的检测精度，但也对探针材料提出了水溶、靶向等复合功能化的需求。本项目拟通过化学修饰的方法，分别设计合成水溶性、靶向作用、荧光示踪的降冰片烯单体，采用Grubbs催化剂通过开环易位聚合的方式直接得到具有复合功能的高分子材料，利用荧光基团实现多谱段/信道下的光学影像示踪，利用靶向片段识别肝癌、肺癌、宫颈癌细胞，甚至是不同细胞器，实现特异性的荧光成像，在细胞层面上实现对癌变的识别，发展具有实际应用前景的新型多功能生物相容高分子材料。

癌症，又称恶性肿瘤，是当今威胁人类健康和生命最严重的疾病之一，早期发现并及时治疗是战胜癌症的首要问题。传统的癌症检测方式受到体内代谢产物浓度太低的限制，很多特异性指标检测精度不高；而基于微观细胞层面的荧光成像技术，能够实现对癌变组织或细胞的可视化灵敏检测，有可能大大提高早期癌症特异性指标的检测精度，但也对探针材料提出了水溶、靶向等复合功能化的要求。本项目通过模块化的聚合物设计方式，发展了一类具有水溶、靶向、示踪、甚至是治疗等复合功能于一体的聚降冰片烯高分子材料，并用于癌细胞的荧光成像。通过化学修饰的方法，设计合成了含有螺吡喃、罗丹明、萘酰亚胺、丹酰胺等各种荧光基团的降冰片烯单体，涵盖了蓝绿、绿、黄、橙黄、橙、橙红、红等可见光谱段，并以之为示踪模块；设计合成了不同链长、不同连接链段的聚乙二醇降冰片烯单体，并以之为水溶性模块；设计合成了RGD、FxrFxK、SV40、TAT的多肽降冰片烯单体，并以之为靶向模块；通过开环易位聚合“一锅法”随机共聚制备了多种功能化水溶性荧光探针高分子，发展了TFA脱保护再渗析纯化等标准的聚合后处理方式；在Bel-7402、HepG2、MCF-7、A549等多种癌细胞中实现了双光子荧光成像，并在线粒体、溶酶体、核仁等不同细胞器实现了特异性荧光成像，发展了一系列具有应用前景的新型聚降冰片烯高分子材料。