| 基于功能化介孔硅纳米材料的miRNA超灵敏检测 |
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| 基金项目:国家重点研发计划项目（2019YFC1805600）；国家自然科学基金项目（21874012，21974010） |
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| 中文摘要:该文基于硅基纳米材料良好的生物安全性，且形貌、尺寸、比表面积、孔径和功能化均较易调控等优势，构建了一种以适配体为靶点的纳米材料作为载体进行肿瘤细胞内试剂递送，并进行了miRNA的超灵敏检测及药物可控释放。由于表面存在硅烷醇基团，使得硅基纳米材料易于氨基化，进一步提高了药物的治疗效果，减少了副作用。首先制备了55 nm的介孔纳米二氧化硅（MSNs），随后在MSNs的介孔中负载阿霉素（Dox），然后通过静电作用将发夹G-四链体DNA （HG1、HG2）包覆在MSNs上，形成DNA门以防止Dox泄露。当靶标miRNA－21存在时，会引发HG1和HG2循环扩增反应，miRNA－21识别HG1并与之杂交，使HG1产生单链尾，该单链尾处于游离状态并增加了其在MSNs上的流动性，促进了与HG2的杂交。HG2可与未展开的HG1结合并启动发夹组装，形成双链G-四链体DNA。基于标记的荧光信号实现了靶标的响应信号放大，与此同时，该扩增反应作为释放Dox的专有钥匙，可通过miRNA－21与HG1和HG2在MSNs表面的杂交来实现药物Dox的可控释放。该功能化纳米材料可实现对癌症标志物miRNA－21的高特异性、高灵敏检测，检出限为0.04 nmol/L。通过纳米材料的靶向递送，可达到最大的治疗效果和最小的副作用。该纳米材料作为一种多功能诊疗一体化的复合纳米材料，在疾病诊疗中具有一定应用前景。 |
| 中文关键词:介孔二氧化硅 循环扩增 可控释放 miRNA |
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| Ultrasensitive Detection of miRNA Based on a Biofunctionalized Mesoporous Silica Nanomaterial |
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| Abstract:Nanomaterials have exhibited great potentials in the field of biological diagnosis and treatment．Recently，the design of an ideal drug delivery system with targeted recognition and controlled release，especially triggered by exclusive endogenous stimulus，has obtained great attentions．Meanwhile，silica based nanomaterials have attracted tremendous attention in biomedical applications in the past decades due to their superior biocompatibility and controllable structures．Developing a silica based nanoparticles mediated drug delivery system for transporting therapeutics to targeted sites and releasing them on demand has been one of most exciting research topics．Herein，the silica nanoparticles were selected for the construction based on the mesoporous silica nanoparticles’ advantages such as good biosafety and easy regulations on morphology，size，specific surface area，tunable pore sizes and easy functionalization．In addition，the surface of the material is easily functionalized due to the presence of silanol groups on the surface，which further improves the therapeutic effect of drugs and reduces the side effects．In this work，an aptamer-targeted silicon nanomaterial was constructed as a carrier for intracellular reagent delivery，ultra-sensitive detection of miRNA and controlled drug releases．Mesoporous silica nanoparticles（MSNs） at 55 nm were firstly prepared for the following functionalization and loadings by traditional st?ber method．Thereafter，the hollow structure of MSNs was loaded with the anticancer drug doxorubicin（Dox）．In addition，the hairpin G－quadruplex DNA（HG1，HG2） was modified on the MSNs by electrostatic action to form a DNA gate to prevent the leaking of Dox．Therefore，in the tumor cells with the presence of miRNA－21 target，the cyclic amplification was triggered with HG1 and HG2．HG1 was employed to recognize and hybridize with miRNA－21，producing a single stranded tail in HG1，which dissociated and increased the mobility of HG1 on MSNs，facilitating its hybridization with HG2．HG2 met unfolded HG1 and initiated hairpin assembly，yielding double strand G－quadruplex（dsG） DNA to result in the signal amplification for the sensitive target detections．In this process，miRNA－21 could also serve as an exclusive key to release Dox by competing against DNA on surface of MSNs．This was achieved by the fully hybridization of miRNA－21 with HG1 and HG2 on MSNs surface，which thereby triggered on-command release of Dox from Dox@MSNs－DNA．As a result，the limit of the detection was 0.04 nmol/L for miRNA－21 detection．Therefore，maximum therapeutic efficacy and minimum side effects were achieved by virtue of the aptamer-targeted delivery and miRNA-targeted drug release．Endowed with highly specific and sensitive detection and controllable release of drugs，this multifunctional nanomaterial show a certain potential in diagnosis and treatment. |
| Key Words:mesoporous silica nanoparticles cyclic amplification controlled release miRNA |
| 引用本文：李晶晶,吴丹,欧阳津,那娜.基于功能化介孔硅纳米材料的miRNA超灵敏检测[J].分析测试学报,2022,41(1):71-77. |
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