具有基因载体功能的光开关近红外荧光聚合物纳米材料设计合成与生物成像研究

Nowadays, photoswitchable fluorescent materials have gained many attentions, owe to they possess broad applications in super-resolution imaging and biomedicine etc. However, the fluorescence emissions of the most of recent photoswitchable fluorescent materials are focused on the visible light region and they can’t be used as gene vector. How to design and synthesize photoswitchable near-infrared fluorescent polymeric nanomaterials (NIR-PFPN) with outstanding properties and further broaden their functions and application fields is an important research direction at present. By combining the principle of fluorescence resonance energy transfer, and using the near-infrared perylene imide fluorophore as the donor and “core”, the amphiphilic star copolymers containing hydrophobic chains with spirothiopyran units (acceptor) and cationic hydrophilic amino chains (as gene vector) are prepared by using the "core-first approach" method. The relationship between the structure of the star copolymers with the photoswitch performance was systematically analyzed and summarized, which helps the design and optimization of the structure and ratio of donor-acceptor, as well as the number of arms, the component and length of hydrophilic and hydrophobic chain with star copolymers. Thus, a series of NIR-PFPNs with excellent photoswitch fluorescence performance are prepared. After further investigating the plasmid DNA binding capacity with the obtained NIR-PFPNs, and studying their applications in near-infrared fluorescent reversible bioimaging and gene transfection efficiency in vitro, it will provide an important scientific basis for in-depth applications of super-resolution imaging and gene vector etc.

光开关荧光材料在超分辨率成像和生物医学等领域展现出广阔的应用前景而备受关注。然而目前该类材料的荧光发射大多在可见光区，且未具备基因载体功能，设计合成性能突出的光开关近红外荧光聚合物纳米材料（NIR-PFPN），并进一步拓展其功能和应用范围是该领域的重要发展方向。本项目结合荧光共振能量转移原理，以近红外苝酰亚胺荧光团为给体和“核”，采用“先核后臂”法制备含螺噻喃基团（受体）的疏水链段和氨基阳离子亲水链段（作为基因载体）的两亲性星形共聚物。通过对星形共聚物的结构与光开关性能之间的关系进行系统的分析与归纳，并反馈于给体-受体结构及比例和星形共聚物臂数、亲疏水链段组成及长度设计优化，以制备出系列具有突出光开关荧光性能的NIR-PFPN。通过进一步考察其与质粒DNA的结合能力，并研究其在体外细胞中的近红外荧光可逆生物成像和基因转染效率，为其在超分辨率成像和基因载体等领域的深入应用提供重要的科学依据。

以聚合物为基质的光开关荧光纳米材料和荧光纳米传感器在生物成像、光学信息存储与加密、生物传感和疾病诊断与治疗等领域具有非常重要的应用价值而备受关注。本项目以聚合物为主要基质，基于荧光共振能量转移（FRET）等原理，采用RAFT聚合、细乳液聚合和共沉淀等方法构筑了系列新型光开关近红外、多色或多态荧光聚合物纳米材料和系列基于离子、pH、温度或生物活性物质等刺激响应性的新型荧光聚合物纳米传感器。系统深入地探索了聚合物纳米体系中聚合物组成结构、各生色团的配比及浓度与体系荧光信号变化的依赖关系、FRET作用机制与能量转移效率优化等问题，并将它们用于生物成像、基因输送与治疗、光学加密防伪和疾病相关物质检测等领域。本项目所取得的成果为智能响应性荧光纳米材料的设计合成与应用提供了新的思路和科学依据。项目原预期在国内外重要专业期刊上发表论文8-12篇，申请中国专利4-6项；实际发表SCI论文27篇（影响因子大于5的有18篇），国内期刊论文2篇，申请中国发明专利15项（已获授权11项），并获得了2020年湖南省自然科学二等奖1项和培养毕业了8位研究生，在成果方面超出了预期计划。

内容获取失败，请点击重试