基于表面增强拉曼光谱技术的肿瘤标志物检测进展

Advances in tumor marker detection using surface-enhanced Raman spectroscopy

肿瘤标志物是反映肿瘤发生情况的物质,与肿瘤诊断、治疗与监测息息相关,肿瘤标志物检测是肿瘤早期筛查的有效手段.随着精准医疗时代来临,对肿瘤标志物检测技术的要求不断提高,表面增强拉曼光谱(surface-enhanced Raman spectroscopy,SERS)技术利用纳米粒子间的局域表面等离激元共振效应,增强分子光谱信号,提高检测灵敏度和准确度,成为了肿瘤标志物检测技术研究的热点,在生物医学、临床诊断等领域具有极大发展潜力.本文以组织检测和液体活检为分类,综述了近5年基于SERS肿瘤标志物检测的研究进展,并提出了通过样品处理、基底改进和探针制备等方式提升标志物检测灵敏度、特异性的思路.同时,本文对SERS技术在临床应用中面临的挑战和发展进行了分析与展望,以期开发出更具潜力的检测技术.

A tumor is a severe threat to human life and health.Tumor markers are usually found in tissues,serum,and other body fluids.These markers reflect tumor occurrence and are closely associated with their diagnosis,treatment,and monitoring.Tumor marker detection is an effective method for early tumor screening.Early tumor screening can save patients time and is the key to tumor prevention and treatment.With the advancement of precision medicine,tumor marker detection technology requirements are constantly increasing,and it is of great significance to develop a convenient,sensitive and accurate method for detecting tumor markers.Utilizing localized surface plasmon resonance(LSPR)among nanoparticles enhances the spectral signals of molecules,thereby improving detection sensitivity and accuracy,surface-enhanced Raman spectroscopy(SERS)technology is a powerful tool and a hot spot in tumor marker detection research with potential in biomedicine,clinical diagnosis,and other fields.The current paper reviews the research progress of SERS in the field of tumor marker tissue detection and liquid biopsy in the past five years.Moreover,the study proposes new ideas to improve the sensitivity of biomarker detection with sample processing,base improvement,and probe research.(1)Using specific adsorption materials and membrane separation technology to optimize the sample and reduce the influence of sample matrix in SERS detection.(2)Absorbing targeted marker molecules with specific probes of antibodies and DNA aptamer to improve the detection specificity and reduce the excessive diagnosis cases due to high sensitivity.(3)Researching the structure,measurement,and size of metal nanoparticles of the base to generate more spots and improve sensitivity.(4)Incorporating other fields like electrochemistry to make up for the SERS detection defect.Meanwhile,we analyzed and prospected the challenges and development of SERS technology in clinical application.Attention should be paid to the stability and biocompatibility of SERS labels,substrate reproducibility,and cost.In practical application,it is necessary to consider the cost-benefit,service cycle,and ease of handling of SERS substrate.Therefore,the research scholar should continue identifying materials that can replace gold,silver,and other nanoparticles.Moreover,a renewable substrate can be prepared to reduce the cost and enhance the stability of the experimental results.SERS technology has a short exploration time in the clinical application stage and requires significant clinical verification and promotion.In the future,predicting potential tumor markers and detecting multiple tumor markers combined with applying the advantages of SERS technology could provide high sensitivity and accuracy.Meanwhile,producing portable sensors for POCT may become a research trend.Thus,it will also provide clinical significance for detecting tumor markers.Sensors developed by SERS technology are of great significance for clinical tumor marker detection.The abovementioned factors can be fully considered and overcome when developing new detection technologies.In that case,the developed sensors will be more widely used for clinical diagnosis,food safety,and environmental protection,among other fields.