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基于CHA信号放大策略的金@铂@HP1-HP2@四氧化三铁纳米酶复合物用于肝癌中循环肿瘤DNA的超灵敏表面增强拉曼散射检测

Au@Pt@HP1-HP2@Fe3O4 Nanoenzymatic Complexes Based on CHA Signal Amplification Strategy for Ultrasensitive SERS Detection of ctDNA in Liver Cancer.

作者信息

Wang Xiaoyong, Sheng Jinxin, Yang Haifan, Shen Kang, Yao Jie, Qian Yayun, Chen Gaoyang

机构信息

Department of General Surgery, Nantong Haimen People's Hospital, Nantong, Jiangsu, People's Republic of China.

Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu, People's Republic of China.

出版信息

Int J Nanomedicine. 2025 Jul 8;20:8891-8905. doi: 10.2147/IJN.S531541. eCollection 2025.

DOI:10.2147/IJN.S531541
PMID:40657480
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12255329/
Abstract

PURPOSE

Early diagnosis of liver cancer requires highly sensitive detection of biomarkers. This study aims to develop a novel method for detecting circulating tumor DNA (ctDNA) in the serum of liver cancer patients, leveraging a catalytic hairpin self-assembly (CHA) signal amplification strategy combined with surface-enhanced Raman scattering (SERS) technology and nano-enzyme catalysis.

METHODS

We synthesized Au@Pt@HP1-HP2@FeO nano-enzyme complexes, utilizing the SERS-enhancing properties of Pt-coated Au nanoparticles (Au@Pt) and the separation-enrichment capability of FeO magnetic beads. The complexes catalyzed the oxidation of colorless TMB by HO to produce blue ox-TMB, enabling quantitative detection of PIK3CA E542K mutant ctDNA. The assay's performance was validated using gold standard qRT-PCR.

RESULTS

Under optimized conditions, the method achieved a detection limit for PIK3CA E542K as low as 4.12 aM. The assay demonstrated high sensitivity, specificity, and efficient magnetic separation, making it a robust tool for ctDNA detection.

CONCLUSION

This study presents a highly sensitive and specific detection platform for liver cancer early diagnosis, characterized by magnetic separation and nano-enzyme catalysis. The method holds significant clinical potential for the accurate and early detection of liver cancer biomarkers.

摘要

目的

肝癌的早期诊断需要对生物标志物进行高度灵敏的检测。本研究旨在开发一种新方法，利用催化发夹自组装（CHA）信号放大策略结合表面增强拉曼散射（SERS）技术和纳米酶催化，检测肝癌患者血清中的循环肿瘤DNA（ctDNA）。

方法

我们合成了Au@Pt@HP1-HP2@FeO纳米酶复合物，利用包覆铂的金纳米颗粒（Au@Pt）的SERS增强特性和FeO磁珠的分离富集能力。该复合物催化HO将无色的TMB氧化为蓝色的ox-TMB，从而能够对PIK3CA E542K突变型ctDNA进行定量检测。使用金标准qRT-PCR验证了该检测方法的性能。

结果

在优化条件下，该方法对PIK3CA E542K的检测限低至4.12 aM。该检测方法具有高灵敏度、高特异性和高效磁分离能力，是一种用于ctDNA检测的强大工具。

结论

本研究提出了一种用于肝癌早期诊断的高灵敏度和特异性检测平台，其特点是磁分离和纳米酶催化。该方法在准确早期检测肝癌生物标志物方面具有巨大的临床潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/9d211985f8bd/IJN-20-8891-g0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/c7e45a479ab1/IJN-20-8891-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/ce6433453e94/IJN-20-8891-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/26d49e7aeb0b/IJN-20-8891-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/0e1346f30c91/IJN-20-8891-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/0dbedde8ca35/IJN-20-8891-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/50dd7ecc29d0/IJN-20-8891-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/ba304185f8c2/IJN-20-8891-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/a229f30c844b/IJN-20-8891-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/60d659d18ee9/IJN-20-8891-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/9d211985f8bd/IJN-20-8891-g0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/c7e45a479ab1/IJN-20-8891-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/ce6433453e94/IJN-20-8891-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/26d49e7aeb0b/IJN-20-8891-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/0e1346f30c91/IJN-20-8891-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/0dbedde8ca35/IJN-20-8891-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/50dd7ecc29d0/IJN-20-8891-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/ba304185f8c2/IJN-20-8891-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/a229f30c844b/IJN-20-8891-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/60d659d18ee9/IJN-20-8891-g0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb57/12255329/9d211985f8bd/IJN-20-8891-g0010.jpg

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