Simultaneous and Spatial Quantification of Telomerase Activity and DNA Methylation in Living Cells by a Deformable Satellite Nanocapsule

作     者：Shan Huang Cheng Ma Jiahao Lin Wenjing Wang Yizhu Xu Xingxin Wu Jian-Rong Zhang Jun-Jie Zhu 

作者机构：School of Chemistry and Chemical EngineeringState Key Laboratory of Analytical Chemistry for Life ScienceNanjing UniversityNanjingJiangsu 210023 College of ScienceState Key Laboratory of Agricultural MicrobiologyHuazhong Agricultural UniversityWuhanHubei 430070 School of Life SciencesState Key Laboratory of Pharmaceutical BiotechnologyNanjing UniversityNanjingJiangsu 210023 School of Chemistry and Life ScienceJinling CollegeNanjing UniversityNanjingJiangsu 210089 

出 版 物：《CCS Chemistry》 (中国化学会会刊（英文）)

年 卷 期：2021年第3卷第4期

页      面：1231-1244页

学科分类：07[理学] 070205[理学-凝聚态物理] 0703[理学-化学] 0702[理学-物理学] 

基　　金：The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China(nos.21834004 and 21904063) the Natural Science Foundation of Jiangsu Province(no.BK20190279). 

主　　题：telomerase DNA methylation simultaneous detection single-cell level the efficacy of anticancer drugs 

摘      要：Telomerase plays an essential role in many biological processes.DNA methylation regulates the expression of many genes,including telomerase.Here,we propose a deformable satellite nanocapsule fluorescein isothiocyanate(FITC)-hollowbowl mesoporous organicsilica@gold nanoparticles-methyl-CpG-binding protein 2(MECP 2)-silver nanoclusters(FHBMO@AMA),for simultaneous quantitative detection of both cytoplasmic telomerase activity and the degree of DNA methylation.This strategy enabled spatial-based detection in cells.The total cytoplasmic telomerase activity was detected by fluorescence energy resonance transfer(FRET)between FHBMO and gold nanoparticles(Au NPs),while the DNA methylation in the nucleus was detected by enhanced fluorescence of silver nanoclusters(Ag NCs).Furthermore,FHBMO@AMA could intuitively distinguish between the differences in telomerase expression in cells during the DNA synthesis period at the mitotic phase(S/M)of the cell cycle.Interestingly,the ratio of the two detections(telomerase activity/DNA methylation)significantly correlated with the efficacy of anticancer drugs.At the same time,there was no apparent linear relationship between any single detection target and the efficacy of the anticancer drugs.Therefore,based on the relationship between telomerase activity and DNA methylation,our newly developed approach serves as new and feasible method for evaluating the efficacy of anticancer drugs,thereby,extending the technology toolbox for precision in medical and pharmaceutical analysis of drug potency.