水溶性D-A-D型共轭大分子的设计、合成及在生物医药领域的应用

共轭聚合物（CPE）在分子检测、细胞成像、抗菌等研究领域有很好的应用前景，得益于其优异的光学性质。然而，CPE骨架的不可降解性会带来难以预知的生物安全性问题，影响CPE在细胞和活体领域的进一步研究。从分子结构上寻求根本解决CPE安全性问题的方法对于推动CPE在医药材料领域的发展具有重要意义。 本项目拟从两个途径解决上述CPE存在的关键问题：1）设计一系列光学性能优异的水溶性D-A-D型共轭寡聚物，以降低细胞毒性方面的风险；2）设计近红外或双光子成像性能突出的水溶性D-A-D型共轭寡聚物的可降解交联体纳米粒子，以避免共轭大分子在细胞和活体代谢器官的蓄积毒性作用。 本项目设计了以下在医药材料领域的初步应用：发展一氧化氮的检测、细胞成像（包括双光子成像）技术，为进一步研究开展基于共轭大分子体系的药物靶向输送以及肿瘤抑制的研究提供基础。

Conjugated polyelectrolytes (CPEs) are promising in applications such as molecular detections, cellular imaging and antibiotic therapy, thanks to their unique optical properties. However, the non-degradability of CPE backbones seriously hurdles their further development in the cellular and animal studies due to the potential unexpected cyto-toxicity. Consequently, it's of extreme importance to work out a way to basically resolve the safety issues of CPEs and promote bio-applications of CPEs by rational design of molecular architecture. In this proposal, two strategies aiming to resolve the crucial issue associated with biocompatibility of CPEs are described: 1) a series of water-soluble D-A-D type conjugated oligomers with outstanding optical properties are structurally designed to diminish the risk of undesired cyto-toxicity, and 2) degradable nanoparticles, formed by crosslinking water-soluble D-A-D type conjugated oligomers with environmentally responsive linkers, are designed with near infrared or two-photon imaging properties to avoid undesired accumulation of macromolecules in metabolic organs such as liver, kidney and spleen. This proposal also depicts three arms of D-A-D oligomers and their crosslinking nanoparticles in biomedical applications: 1) to establish in vitro and in vivo nitric oxide delivery systems; 2) to develop detection method, cellular and animal imaging techniques for nitric oxide (two photon imaging technique included), and 3) to explore combination of nitric oxide delivery and nano-medicine for in vivo tumor inhibition.