用于乳腺癌诊疗一体化的含卟啉荧光聚合物纳米体系研究

Breast cancer is one of the most common malignant tumors in women. The design of accurate diagnosis and efficient therapeutics of breast cancer is of great significance. Porphyrin, as an excellent fluorescent probe or photosensitizer, has been used for detection of tumor biomarkers or photodynamic therapy. However, it is difficult to carry out multi-functional modification of porphyrin-based small molecules, and enable them both detection and therapeutics functions. In contrast, the polymer system exhibits the advantages of multiple structures, flexible design, etc, and has been served as an ideal matrix for constructing the integration of diagnosis and therapeutics. In present study, by using porphyrin chain transfer agent as the reference fluorophore and photosensitizer, the perfluorinated compound as both the oxygen carrier and hydrophobic segment, polyethylene glycol, sulfatase-responsive fluorophore and cancer cells targeting group as the hydrophilic segment, the amphiphilic block copolymer with multiple functions are prepared by combining of reversible addition-fragmentation chain transfer radical polymerization (RAFT) and click chemistry. After further optimize the number of arms and functional groups, the proportion of hydrophilic and hydrophobic segments, and the molecular weight of block copolymers, novel porphyrin-based fluorescent polymeric nanoparticle with both ratiometric detection for sulfatase and efficient auto-oxygenation photodynamic therapy characteristics are synthesized via using reprecipitation method, to achieve accurate diagnosis and efficient therapeutics of breast cancer. This strategy can provide new ideas for the precise theranostics of cancer.

乳腺癌是女性最常见的恶性肿瘤之一，开展乳腺癌的准确诊断和高效治疗一体化研究意义重大。卟啉作为一种性能优良的荧光探针或光敏剂，已用于肿瘤标志物检测或光动力治疗。但基于卟啉的小分子体系难以进行多功能修饰而兼具检测和治疗功能；相对而言，高分子体系结构多样、设计灵活，是构建各种诊疗一体化体系的理想基质。本项目以作为参比荧光团和光敏剂的卟啉链转移剂为起点，全氟化物为氧气载体和疏水链段，以聚乙二醇、硫酸酯酶响应荧光团和癌细胞靶向基团为亲水链段，采用可逆加成-断裂链转移自由基聚合(RAFT)和点击化学法相结合，构建集多种功能于一体的两亲性嵌段共聚物；优化设计嵌段共聚物的臂数、功能基团数量、亲疏水链段比例及分子量等，利用再沉淀法制备兼具硫酸酯酶比率荧光响应和自供氧高效光动力治疗特征的靶向含卟啉的荧光聚合物纳米体系，实现对乳腺癌的准确诊断和高效治疗，为癌症的精准诊疗一体化研究提供新思路。

高性能的响应性荧光/光电传感器和光开关荧光材料在生物成像、指纹显影、荧光防伪与加密等领域具有重要的应用价值而备受广泛关注。本项目通过合理的分子设计，基于荧光共振能量转移（FRET）等原理，采用多种官能团修饰、可逆加成断裂链转移（RAFT）聚合、共沉淀、自组装和表面接枝等手段，构筑了系列性能优良的新型响应性荧光/光电传感器和光开关多态荧光聚合物纳米材料，系统深入地探索材料的组成、结构与性能之间的关系，并将它们成功应用于生物成像、环境检测、荧光防伪与加密等领域。本项目所取得的成果将为智能响应性荧光/光电材料的设计合成与应用提供了新的理论依据。从项目立项至今，已先后在ACS Applied Materials & Interfaces、Materials Chemistry Frontiers、ACS Sensors等国际国内学术期刊上发表相关学术论文16篇，其中影响因子大于6.0的论文7篇。申请中国发明专利8件（其中授权4件）。项目资助期内部分代表性成果获得了2020年湖南省自然科学二等奖1项，培养硕士毕业生6人，顺利完成并超出了预期的研究成果。