基于G-四链核酸模拟酶的靶向自发光光动力学体系在癌症治疗中的应用

Cancer treatment is gaining extreme interest and becoming a research hotspot due to health threats caused by cancer. Photodynamic therapy (PDT) is one of the most promising modalities for the treatment of cancer. PDT utilizes the fact that photosensitizers are capable of generating cytotoxic reactive oxygen species (ROS) to kill tumor cells when exposed to light of specific wavelength. Although many studies in the application of PDT have been reported, some challenges still persist, including poor water solubility of photosensitizers, limited tissue penetration depth of the excitation light, and low specific recognition toward target cells. Therefore, the efforts focused on the preparation of new systems for PDT are required. Herein, we propose to construct a new targeted and self-illuminated PDT system based on the unique properties of catalytic G-quadruplexes, chemiluminescence, mesoporous silica nanoparticles (MSNs) and the specific recognition ability of aptamer toward cancer cells. Reactive oxygen species can be generated to kill cancer cells without the outer light source. Furthermore, in vivo therapy will be carried out to demonstrate the PDT effects on the tumor-bearing mouse model. Meanwhile, to further confirm the effects on the tumors and non-toxicity to other organs, histological examination will be performed. A solution to these problems discussed above would be a major advance in PDT. Most importantly, the system can work in vivo even in the deeper tissue, which will overcome the drawback of the deep tissue penetration for PDT with light irradiation. Our study will provide theoretical basis and technical support in the field of photodynamic therapy for cancer in the future.

癌症治疗是世界共同关注的研究课题。光动力学治疗是近些年发展起来的一种治疗癌症和其它疾病的重要方法。它是利用光和光敏试剂在有氧条件下产生活性态氧，从而破坏病变细胞和组织的疗法。目前已有不少相关报道。但是光敏试剂的疏水性、对靶点的非特异性以及光源有限的组织穿透能力限制了光动力学治疗的应用。因此需要发展新型光动力学治疗体系。本课题预备结合G-四链核酸模拟酶的催化性质、化学发光技术、核酸适体的特异性识别性质以及介孔二氧化硅纳米粒子的特性，构建新型的靶向自发光光动力学治疗体系，在不需要外加光源情况下，用于癌症的治疗。此外构建动物模型，对实体瘤进行治疗。并且证明该体系除了作用于癌组织，对其它器官不产生明显毒性。从而解决光敏剂疏水性问题，提高对癌细胞靶点的识别，最重要的是，在无外加光源条件下进行深层组织下的肿瘤治疗，克服以往光源穿透力弱的缺点，为今后高效、高特异性的癌症光动力治疗提供理论基础和实验支持。

由于癌症成为严重威胁人类健康的主要疾病之一，癌症治疗成为世界共同关注的研究课题。光动力学治疗是近些年发展起来的一种治疗癌症和其它疾病的重要方法。但是在实际应用过程中，光敏试剂的疏水性、对靶点的非特异性以及光源有限的组织穿透能力限制了光动力学治疗的应用。因此需要构建新型的光动力学治疗体系。本项目按照预定计划实施，经过三年的工作，取得了重要的研究进展和一系列成果。主要研究内容为：（1）构建了基于核苷酸的药物运载/释放、细胞成像及捕光体系。（2）构建了基于核酸的疾病相关标志物的检测体系，用于巯基及端粒酶的快速、高灵敏、高选择性检测。（3）构建近红外光辐射的光热、光动力学癌症治疗体系。（4）构建了基于核酸的药物运载体系和生物信息处理体系。三年内一共发表SCI收录论文18篇，其中包括Angew. Chem. Int. Ed. 1篇，Adv. Mater. 2篇。这些工作为今后高效、高特异性的癌症光动力治疗提供理论基础和实验支持。