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一种新型、安全、快速且靶向的红色碳点探针用于识别叶酸酶高表达肿瘤的研究

study of a novel, safe, rapid, and targeted red carbon dot probe for recognition of tumors with high expression of folate enzyme.

作者信息

Zhong Zhuoling, Li Xingying, Liu Shuyao, Zhang Chuanwei, Xu Xiaoping, Liao Liyun

机构信息

West China School of Pharmacy, Sichuan University Chengdu 610041 China

Chengdu Med Coll, Sch Pharm 783, Xindu Ave Chengdu 610500 China

出版信息

RSC Adv. 2021 Sep 10;11(46):28809-28817. doi: 10.1039/d1ra04592j. eCollection 2021 Aug 23.

Abstract

Carbon dots (CDS) have been proved to be a type of ideal biological imaging probe. They have the advantages of spontaneous fluorescence, anti-photobleaching, good biocompatibility and easy surface decoration, and are receiving special attention from researchers. The early imaging diagnosis of tumors has always been a practical means of clinical diagnosis. Finding an efficient and low-toxicity tumor probe is the continuous goal of tumor clinical diagnosis and treatment. Therefore, this article uses the modifiable properties of the surface structure of carbon dots, and at the same time, uses the characteristics of tumors with high expression of folate receptors (FR) that can specifically take up folic acid (FA) to construct folic acid carbon dot conjugates (FA-CDs) to achieve targeted tumor uptake. Firstly, CCK8 toxicity tests proved that FA-DCCDs had good biocompatibility and were almost non-toxic. Further, confocal cell imaging experiments, microplate quantitative experiments and flow cytometry experiments proved that FA-CDs were selective and more easily absorbed by tumor cells with high expression of folate receptors, and bare carbon dots could be absorbed into cells without selectivity. Through experiments, the law of injection of bare CDs into the body was explored, which proved that they had no obvious accumulation and had high distribution in the liver and kidneys. FA-CDs was applied to the targeted imaging of a mouse tumor model for the first time, which proved again that the carbon point coupled with folic acid had selectivity for tumor cells with high expression of FR receptors, which provided a basis for tumor drug research and early clinical diagnosis of tumors.

摘要

碳点(CDs)已被证明是一种理想的生物成像探针。它们具有自发荧光、抗光漂白、良好的生物相容性和易于表面修饰等优点,受到研究人员的特别关注。肿瘤的早期成像诊断一直是临床诊断的实用手段。寻找一种高效、低毒的肿瘤探针是肿瘤临床诊断和治疗的持续目标。因此,本文利用碳点表面结构的可修饰特性,同时利用叶酸受体(FR)高表达的肿瘤能够特异性摄取叶酸(FA)的特点,构建叶酸碳点缀合物(FA-CDs)以实现肿瘤靶向摄取。首先,CCK8毒性试验证明FA-DCCDs具有良好的生物相容性且几乎无毒。进一步的共聚焦细胞成像实验、微孔板定量实验和流式细胞术实验证明,FA-CDs具有选择性,更容易被叶酸受体高表达的肿瘤细胞吸收,而裸碳点可无选择性地被细胞吸收。通过实验,探索了裸碳点注入体内的规律,证明它们没有明显的蓄积,在肝脏和肾脏中分布较高。首次将FA-CDs应用于小鼠肿瘤模型的靶向成像,再次证明叶酸偶联的碳点对FR受体高表达的肿瘤细胞具有选择性,为肿瘤药物研究和肿瘤早期临床诊断提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba57/9038144/019e7d8c9c57/d1ra04592j-s1.jpg

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