A Supersensitive CTC Analysis System Based on Triangular Silver Nanoprisms and SPION with Function of Capture, Enrichment, Detection, and Release,ACS Biomaterials Science & Engineering

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A Supersensitive CTC Analysis System Based on Triangular Silver Nanoprisms and SPION with Function of Capture, Enrichment, Detection, and Release
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2018-02-05 00:00:00 , DOI: 10.1021/acsbiomaterials.7b00825
Huimin Ruan _{1,

2} , Xiaoxia Wu ₁ , Chengcheng Yang ₃ , Zihou Li ₁ , Yuanzhi Xia ₁ , Ting Xue ₁ , Zheyu Shen _{1,

4} , Aiguo Wu ₁

Affiliation

Detection of circulating tumor cells (CTCs) may be applied for diagnosis of early tumors like a liquid biopsy. However, the sensitivity remains a challenge because CTCs are extremely rare in peripheral blood. In this study, we developed a supersensitive CTC analysis system based on triangular silver nanoprisms (AgNPR) and superparamagnetic iron oxide nanoparticles (SPION) with function of capture, enrichment, detection, and release. The AgNPR was encoded with MBA (i.e., 4-mercaptobenzoic acid) and modified with rBSA (i.e., reductive bovine serum albumin) and FA (i.e., folic acid) generating organic/inorganic composite nanoparticle MBA-AgNPR-rBSA-FA, which has the function of surface-enhanced Raman scattering (SERS). The optimized SERS nanoparticles (i.e., MBA3-AgNPR-rBSA4-FA2) can be utilized for CTC detection in blood samples with high sensitivity and specificity, and the LOD (i.e., limit of detection) reaches to five cells per milliliter. In addition, the SPION was also modified with rBSA and FA generating magnetic nanoparticle SPION-rBSA-FA. Our supersensitive CTC analysis system is composed of MBA3-AgNPR-rBSA4-FA2 and SPION-rBSA-FA nanoparticles, which were applied for capture (via interaction between FA and FRα), enrichment (via magnet), and detection (via SERS) of cancer cells from blood samples. The results demonstrate that our supersensitive CTC analysis system has a better sensitivity and specificity than the SERS nanoparticles alone, and the LOD is up to 1 cell/mL. The flow cytometry and LSCM (i.e., laser scanning confocal microscope) results indicate the CTCs captured, enriched, and isolated by our supersensitive CTC analysis system can also be further released (via adding excessive free FA) for further cell expansion and phenotype identification.

中文翻译：

基于三角银纳米棱镜和SPION的具有捕获，富集，检测和释放功能的超灵敏CTC分析系统

循环肿瘤细胞（CTC）的检测可以应用于早期肿瘤的诊断，例如液体活检。但是，由于四氯化碳在外周血中极为罕见，因此敏感性仍然是一个挑战。在这项研究中，我们开发了一种基于三角银纳米棱镜（AgNPR）和超顺磁性氧化铁纳米颗粒（SPION）的超灵敏CTC分析系统，该系统具有捕获，富集，检测和释放的功能。AgNPR用MBA（即4-巯基苯甲酸）编码，并用rBSA（即还原性牛血清白蛋白）和FA（即叶酸）修饰，生成有机/无机复合纳米颗粒MBA-AgNPR-rBSA-FA，其具有表面增强拉曼散射（SERS）的功能。优化的SERS纳米颗粒（即 MBA3-AgNPR-rBSA4-FA2）可用于血液样品中的CTC检测，具有高灵敏度和特异性，并且LOD（即检测极限）达到每毫升5个细胞。另外，还用rBSA和FA修饰了SPION，产生了磁性纳米粒子SPION-rBSA-FA。我们的超灵敏CTC分析系统由MBA3-AgNPR-rBSA4-FA2和SPION-rBSA-FA纳米颗粒组成，可用于捕获（通过FA和FRα之间的相互作用），富集（通过磁体）和检测（通过SERS）血液样本中的癌细胞。结果表明，我们的超灵敏CTC分析系统比单独的SERS纳米颗粒具有更好的灵敏性和特异性，并且LOD高达1细胞/ mL。流式细胞仪和LSCM（即激光扫描共聚焦显微镜）结果表明捕获，富集，

更新日期：2018-02-05

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