近红外光敏感钌聚合物的合成及其在癌症光疗中的应用

Nanoparticle drug-delivery system of photoresponsive polymers have been widely used in cancer phototherapy research. However, recently reported photoresponsive polymers are only sensitive to UV or visible light, which limits their applications for phototherapy in deep tissue. In this proposal we plan to synthesize a near-infrared (NIR) light-responsive Ru complex, and then fabricate NIR light-responsive Ru-containing polymers for anticancer phototherapy. The Ru-containing polymer can assemble into nanoparticles in aqueous solution. These nanoparticles will accumulate in the tumor sites via the enhanced permeability and retention (EPR) effect. NIR light irradiation of the nanoparticles can release anticancer Ru complexes and generate singlet oxygen. The combined photochemotherapy (PACT) and photodynamic therapy (PDT) will demonstrate enhanced antitumor activity. The NIR light-responsive polymer developed in this proposal can be used for cancer treatment in deep tissue, which is of great importance for clinical cancer phototherapy both theoretically and practically.

光敏感聚合物纳米载药体系已被广泛应用于癌症光疗的研究中。然而，目前已报道的光敏感聚合物只对紫外光或可见光响应，不适合深层组织的癌症光疗。本项目拟合成一种对近红外光敏感的钌配合物，并基于此构筑近红外光敏感的钌聚合物用于抗癌光疗。聚合物在水溶液中能自组装成纳米粒子，并可通过血液循环经“增强的渗透和滞留（EPR）”效应聚集在肿瘤部位。在近红外光照射下，纳米粒子将释放出具有抗癌活性的钌配合物以及单线态氧，从而实现光化学与光动力的联合治疗，增强抑瘤效果。本项目开发的近红外光敏感的钌聚合物可用于深层组织的癌症治疗，对于临床癌症光疗具有重要的理论和实际意义。

针对传统光敏感分子及聚合物响应波长短，不适合生物应用的难题，该项目设计、合成新型红光及近红外光敏感的钌配合物，总结出配体共轭结构、供吸电子能力、空间结构等对于钌配合物吸收光谱及光敏感性的影响规律；通过优化配体结构调控钌配合物的光动力及化疗效果；利用钌配合物构筑聚合物体系研究了聚合物体系在水溶液中的自组装行为、肿瘤靶向能力；利用钌聚合物纳米体系实现对小鼠体内肿瘤的光动力及化疗联合治疗。基于该项目资助，共发表相关SCI 论文15篇（标注有本基金号），其中通讯作者论文13篇，第一作者2篇，IF>10的高水平论文9篇；申请国家发明专利5项，其中授权2项；获基金委优秀青年项目资助及中国石油和化学工业联合会技术发明一等奖。