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核酸功能化纳米探针在细胞荧光成像中的应用

郑爱仙 张晓龙 刘小龙

郑爱仙, 张晓龙, 刘小龙. 核酸功能化纳米探针在细胞荧光成像中的应用[J]. 中国光学, 2018, 11(3): 363-376. doi: 10.3788/CO.20181103.0363
引用本文: 郑爱仙, 张晓龙, 刘小龙. 核酸功能化纳米探针在细胞荧光成像中的应用[J]. 中国光学, 2018, 11(3): 363-376. doi: 10.3788/CO.20181103.0363
ZHENG Ai-xian, ZHANG Xiao-long, LIU Xiao-long. Application in nucleic acid functionalized nanoprobe in cellular fluorescence imaging[J]. Chinese Optics, 2018, 11(3): 363-376. doi: 10.3788/CO.20181103.0363
Citation: ZHENG Ai-xian, ZHANG Xiao-long, LIU Xiao-long. Application in nucleic acid functionalized nanoprobe in cellular fluorescence imaging[J]. Chinese Optics, 2018, 11(3): 363-376. doi: 10.3788/CO.20181103.0363

核酸功能化纳米探针在细胞荧光成像中的应用

doi: 10.3788/CO.20181103.0363
基金项目: 

国家自然科学基金项目 21705022

国家自然科学基金项目 21605021

国家自然科学基金项目 61575044

详细信息
    作者简介:

    郑爱仙(1987-), 女, 福建福州人, 博士, 助理研究员, 2009年、2014年于福州大学分别获得学士、博士学位, 主要从事生物标志物的荧光分析与成像方面的研究。E-mail:zax040500273@126.com

    刘小龙(1980-), 男, 四川射洪人, 博士, 研究员, 2003年、2008年于西安交通大学分别获得学士、博士学位, 主要从事肿瘤早期诊断新技术与新方法方面的基础与临床转化方面的研究。E-mail:xiaoloong.liu@gmail.com

  • 中图分类号: O657

Application in nucleic acid functionalized nanoprobe in cellular fluorescence imaging

Funds: 

National Natural Science Foundation of China 21705022

National Natural Science Foundation of China 21605021

National Natural Science Foundation of China 61575044

More Information
  • 摘要: 核酸是携带遗传信息的物质,既存在于自然界中也能够通过成熟技术人工合成。通过体外筛选技术还可以筛选出具有特殊功能的核酸序列,例如核酸适体和脱氧核酶。核酸通过沃森-克里克碱基互补配对原则进行杂交,具有很强的专一性。无论是通过序列设计还是体外筛选,核酸探针在生物标志物的分析与成像应用方面都发挥着重要作用。纳米材料辅助构建核酸功能化纳米探针,可以保护负载的核酸探针不被核酸酶降解,并且无需转染试剂就能进入细胞,在细胞荧光成像应用上具有很大优势。为解决细胞内有些生物标志物含量低、难于检测的问题,目前已构建多种适用于细胞水平的成像信号放大方法来实现对低丰度生物标志物的高灵敏成像。本文主要综述了核酸功能化纳米探针在细胞荧光成像中的应用进展,包括反义寡核苷酸功能化纳米探针、核酸适体功能化纳米探针、脱氧核酶功能化纳米探针等,同时介绍了他们在成像信号放大中的应用。
  • 图  1  (a) 分子信标响应原理;(b)线型核酸探针响应原理

    Figure  1.  (a)Rresponse principle of molecular beacons; (b)Response principle of linear nucleic acid probe

    图  2  (a) 纳米金辅助构建的核酸纳米探针用于细胞内mRNA成像[18];(b)聚多巴胺辅助构建的核酸纳米探针用于成像细胞分化相关的miRNA[19];(c)多色核酸纳米探针用于活细胞内肿瘤相关mRNA成像[20];(d)核酸作为模板合成具有荧光性质的金纳米簇并用于细胞成像[21]

    Figure  2.  (a)AuNPs-based nucleic acid nanoprobe for application in intracellular mRNA imaging[18]; (b)polydopamine-based nucleic acid nanoprobe for the imaging of miRNAs in living human mesenchymal stem cells[19]; (c)a multicolor nanoprobe for imaging of tumor-related mRNAs in living cells[20]; (d)nucleic acid based template for the synthesis of fluorescent gold nanoclusters and their application in cell imaging[21]

    图  3  基于FRET的纳米探针用于细胞内mRNA检测:降低假阳性信号并使系统波动影响最小化[23]

    Figure  3.  FRET nanoprobe for intracellular mRNA detection:avoiding false positive signals and minimizing effects of system fluctuations[23]

    图  4  (a) 核酸纳米探针用于活细胞内miRNA的催化性分子成像[22];(b)细胞内杂交链反应用于放大检测mRNA[26]

    Figure  4.  (a)Catalytic molecular imaging of miRNA in living cells by nucleic acid nanoprobe[22]; (b)intracellular hybridization chain reaction for the amplification detection of mRNA[26]

    图  5  核酸适体筛选过程[28]

    Figure  5.  Schematic presentation of aptamer selection process[28]

    图  6  不同核酸适体探针的响应原理[31]

    Figure  6.  Response principle of different aptamer probes[31]

    图  7  (a) 金纳米棒辅助构建的核酸适体探针用于癌细胞特异性的成像与治疗[37];(b)核酸适体功能化纳米探针用于线粒体释放的细胞色素C的荧光成像[38];(c)AS1411核酸适体与反义寡核苷酸同时功能化的纳米颗粒用于癌细胞内microRNA-221荧光成像[39]

    Figure  7.  (a)Gold nanorods based aptamer switch probes for cancer cell specific imaging and treatment[37]; (b)fluorescence imaging of cytochrome c released from mitochondria using aptameric nanoprobe[38]; (c)fluorescence imaging of microRNA-221 in cancer cells by using nucleolin aptamer and antisense oligonucleotides functionalized nanoparticles[39]

    图  8  (a) 脱氧核酶体外筛选过程;(b)脱氧核酶的结构与切割位点[42];(c)目标核酸诱导活性脱氧核酶的形成[43];(d)核酸适体与目标分子结合诱导活性脱氧核酶的形成[44]

    Figure  8.  (a)Schematic presentation of DNAzyme selection process; (b)structure of DNAzyme and the RNA cleavage site[42]; (c)target nucleic acid induced the formation of an active DNAzyme[43]; (d)binding of aptamer to target molecule induced the formation of an active DNAzyme[44]

    图  9  (a) 活细胞内基于脱氧核酶功能化纳米金的Zn2+和Cu2+同时荧光成像研究[45];(b)核酸适体功能化的脱氧核酶与纳米金结合用于活细胞内目标分子的放大荧光成像[46]

    Figure  9.  (a)Simultaneous fluorescence imaging of Zn2+ and Cu2+ in living cells based on DNAzyme modified gold nanoparticle[45]; (b)aptazyme-gold nanoparticle sensor for amplified molecular probing in living cells[46]

    图  10  (a) 活细胞内miRNA触发脱氧核酶活化[47];(b)纳米金-发夹型脱氧核酶探针用于活细胞内miRNA成像信号放大[48]

    Figure  10.  (a)MicroRNA-initiated DNAzyme activation in living cells[47]; (b)AuNP-based hairpin-DNAzyme probe for amplification detection of miRNA in living cells[48]

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  • 收稿日期:  2018-01-26
  • 修回日期:  2018-02-28
  • 刊出日期:  2018-06-01

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