氮掺杂石墨烯量子点-微生物共轭体系增强靶向肿瘤及可视化生物治疗的研究

Improving the distribution of anticancer drugs in tumors is the key to enhance the therapeutic effect. Some bacteria preferentially colonizing in tumor can be utilized as natural carriers for tumor targeting due to their hypoxia-driving ability. Here, we propose a bionic strategy of “charging” attenuated Salmonella by nitrogen-doped graphene quantum dots (NGQDs) to strengthen their metabolic activities. Under UV light irradiation, photoelectrons produced by NGQDs can be transferred to Salmonella to promote the enzymatic reduction of nitrate ion to cytotoxic nitric oxide for anti-cancer. Meanwhile, the cancer treatment can be monitored via NIR imaging from NGQDs. We choose breast cancer as tumor model and study the tumor-distribution, toxicity and enhanced the effect of photo-induced bacterial metabolite therapy both in vitro and in vivo and its corresponding mechanism of this abiotic-biotic hybrid. It provides a new idea for simple, low toxic and efficient methods of cancer diagnosis and treatment. Our results will provide a new sight for tumor therapy as a novel method with simplicity, low toxicity and high efficiency.

提高抗癌药物在肿瘤中的有效分布对增强肿瘤治疗效应至关重要。为此，申请人提出构建具有乏氧特异性靶向的重组减毒沙门氏菌联合具有特殊光学性质的氮掺杂石墨烯量子点的无机-生物共轭体，实现对肿瘤的高穿透覆盖；通过光照激发氮掺杂石墨烯量子点产生电子转运至减毒沙门氏菌体内的“充电”仿生方式，提高其代谢抗癌试剂一氧化氮达到对肿瘤精准高效治疗的目的；同时，利用氮掺杂石墨烯量子点近红外成像特征，实现对肿瘤的定位与可视化治疗监测。本项目系统研究这种无机-生物共轭体的肿瘤特异性空间分布、安全性、毒理性以及相关的生物化学机理，并选择乳腺癌为模型，通过体外和体内实验阐明其光控增效微生物代谢机制，评估其肿瘤治疗效应，为简单、低毒、高效的肿瘤诊断治疗方法提供新的思路，对探索纳米功能材料与微生物相结合作为一种全新的肿瘤诊治模式也具有一定借鉴意义。

提高抗癌药物在肿瘤中的有效分布对增强肿瘤治疗效应至关重要。因此，我们通过构建具有乏氧特异性靶向的大肠杆菌联合具有特殊光学性质的氮掺杂石墨烯量子点的无机-生物共轭体，实现了对肿瘤的高穿透覆盖；通过光照激发氮掺杂石墨烯量子点产生电子转运至大肠杆菌体内的“充电”仿生方式，提高了其代谢抗癌试剂一氧化氮达到对肿瘤精准高效治疗的目的；同时，利用氮掺杂石墨烯量子点近红外成像特征，实现了对肿瘤的定位与可视化治疗监测；通过体外和体内实验阐明了其光控效微生物代谢机制。此外，氮掺杂石墨烯量子点和大肠杆菌具有较高的安全性，较低的生理毒性，它们的复合体制备工艺简单易行，真正符合肿瘤靶向、低毒、精准治疗的发展趋势，本项目的研究成果有望为肿瘤的治疗开辟一条新的思路。