具有抗癌活性和光学成像功能的稀土纳米颗粒-钌类配合物体系的研究

Nowadays, Cancer is a continuous threat to human being’s health. The theranostic system which based on the anticancer drugs and luminescent probes brings novel approaches to the cancer therapy. The Ruthenium bipyridyl compounds with steric effect(SERubip) has high anticancer activity by light activation and low dark toxicity. Furthermore, it overcomes the disadvantage of the traditional PDT for oxygen dependence. Nevertheless, SERubip are not able to effectively absorb light on the NIR region, which limits the application of SERubip in in-vivo anticancer therapy. Rare earth based nanoparticles (RENPs), on the one hand, could activate the SERubip by up conversion emission; on the other hand, its down conversion emission could be used for NIRII imaging. However, the dual mode RENPs (DMRENPs),which with both high efficient emission on down conversion and up conversion, have rarely been reported. Based on the applicant’s experience on the SERubip、RENPs and bioimaging, the DMRENPs@SERubip nanosystem is proposed. The DMRENPs is developed with independently optimised up conversion and down conversion domain, which, by excitation at 980nm, could activate SERubip for in-vivo anticancer therapy and realize a clear NIRII imaging for deep cancer tissue at the same time. The research on the SERubip@RENPs nanosystem could provide a foundation for clinical research and development of SERubip. The development of DMRENPs could also promote further researches on other theranostic system.

以抗癌药物和发光探针为基础的诊疗系统为癌症治疗提供了新思路。具有空间位阻效应的钌联吡啶类配合物（SERubip）不仅光活化抗癌选择性高、暗毒性低，而且摆脱了光动力学疗法对氧气的依赖，成为诊疗体系的理想选择。然而SERubip有不能在近红外区吸收的不足。稀土纳米颗粒（RENPs）的上转换发光能激发SERubip，其下转换发光能实现诊疗成像。然而同时具有高效双功能发光的RENPs（DMRENPs），目前研究较少。本项目在申请人有关SERubip、RENPs以及生物成像研究的基础上，提出构建DMRENPs@SERubip纳米诊疗体系。DMRENPs具有独立优化的下转换发光核和上转换发光壳层的双功能结构,可以在980nm激发下，通过上转换发光活化SERubip达到活体肿瘤治疗目的，同时利用其下转换近红外二区发光，实现肿瘤的清晰成像，达到实时监控治疗过程目的，为SERubip面向临床开发提供研究基础

癌症成为威胁人类健康生活的首要因素。以抗癌药物和发光探针为基础的诊疗系统为癌症治疗提供了新思路。本项目利用具有空间位阻效应的钌联吡啶类配合物（SERubip），不仅实现了光活化抗癌高选择性、低暗毒性，而且摆脱了光动力学疗法对氧气的依赖。同时本项目利用稀土纳米颗粒（RENPs）的上转换发光能激发SERubip，其下转换发光能实现诊疗成像。构建了DMRENPs@SERubip纳米诊疗体系，DMRENPs具有独立优化的下转换发光核和上转换发光壳层的双功能结构,可以在980nm激发下，通过上转换发光活化SERubip达到活体肿瘤治疗目的，同时利用其下转换近红外二区发光，实现肿瘤的清晰成像，达到实时监控治疗过程目的。本项目对DMRENPs@SERubip纳米诊疗体系的研究不仅为SERubip面向临床开发提供研究基础，而且DMRENPs可以为其他的诊疗体系的提供研究平台。