Profiling of Tumor Cell‐Delivered Exosome by Surface Enhanced Raman Spectroscopy‐Based Biosensor for Evaluation of Nasopharyngeal Cancer Radioresistance

Abstract

Although the advancement of radiotherapy significantly improves the survival of nasopharyngeal cancer (NPC), radioresistance associated with recurrence and poor outcomes still remains a daunting challenge in the clinical scenario. Currently, effective biomarkers and convenient detection methods for predicting radioresistance have not been well established. Here, the surface-enhanced Raman spectroscopy combined with proteomics is used to firstly profile the characteristic spectral patterns of exosomes secreted from self-established NPC radioresistance cells, and reveals specific variations of proteins expression during radioresistance formation, including collagen alpha-2 (I) chain (COL1A2) that is associated with a favorable prognosis in NPC and is negatively associated with DNA repair scores and DNA repair-related genes via bioinformatic analysis. Furthermore, deep learning model-based diagnostic model is generated to accurately identify the exosomes from radioresistance group. This work demonstrates the promising potential of exosomes as a novel biomarker for predicting the radioresistance and develops a rapid and sensitive liquid biopsy method that will provide a personalized and precise strategy for clinical NPC treatment.

Surface‐Enhanced Raman Spectroscopy‐Based Optical Biosensor for Liquid Biopsy: Toward Precision Medicine

“…[ 108 ] Our group combined SERS with proteomics to profile EXOs delivered by cancer cells, well‐identifying EXOs from the radioresistance group via a deep learning–based diagnostic model (Figure 7E). [ 109 ] Indeed, natural imbalances in cancer types are common in populations but are often overlooked leading to the loss of characteristics in minority classes by learning methods. Hence, a power law–based synthetic minority oversampling technique was proposed by our research group to overcome imbalance during the generation of a multiclassification model based on SERS data.…”

Cancer diagnosis using label-free SERS-based exosome analysis

“…Depending on the research purpose and experimental conditions, exosomes may also be isolated from other sources such as fetal bovine serum 54 and bronchoalveolar lavage fluid 31 . It should be noted that cells 23 , 32 - 35 , 37 , 38 , 43 , 46 , 49 , 55 - 60 are also commonly used for discriminative analysis of cancerous and non-cancerous exosomes based on SERS (Figure 1 ). Significant advancements have been achieved in the field of exosome isolation techniques, yielding promising insights into the understanding of exosomes 61 , 62 .…”

“…Nanoparticle tracking analysis (NTA) are commonly used to count and size exosome, which are viewed by the incident illumination coming from laser light 32 , 36 - 40 , 45 - 48 , 50 - 52 , 55 , 57 - 59 , 63 . Transmission electron microscopy (TEM) is used as a compensation to confirm the detection of NTA as it is relatively time-consuming and not fitted for a large amount of exosomes although it can be used to check the quality of preparations in a visualized way 28 , 31 , 33 , 36 - 38 , 40 - 43 , 45 - 47 , 50 , 51 , 53 , 54 , 56 - 60 . Western blotting is an important procedure for exosome characterization to confirm some specific proteins in exosomes 28 , 32 , 33 , 36 , 41 , 43 , 45 , 46 , 48 , 50 , 53 , 54 , 56 - 60 .…”

“…Transmission electron microscopy (TEM) is used as a compensation to confirm the detection of NTA as it is relatively time-consuming and not fitted for a large amount of exosomes although it can be used to check the quality of preparations in a visualized way 28 , 31 , 33 , 36 - 38 , 40 - 43 , 45 - 47 , 50 , 51 , 53 , 54 , 56 - 60 . Western blotting is an important procedure for exosome characterization to confirm some specific proteins in exosomes 28 , 32 , 33 , 36 , 41 , 43 , 45 , 46 , 48 , 50 , 53 , 54 , 56 - 60 . As well as those commonly used techniques, there are some more techniques used for exosome characterization depending on the research purpose before SERS analysis, such as dynamic light scattering 32 , 34 - 36 , 38 , 47 , 60 , zeta potential analyzer 32 , 38 , fluorescence 23 , flow cytometry 43 , 52 , 58 , atomic force microscope 48 , single particle interferometric reflectance imaging sensing 40 , tunable resistive pulse sensing 54 and protein assay kit 60 .…”

“…Western blotting is an important procedure for exosome characterization to confirm some specific proteins in exosomes 28 , 32 , 33 , 36 , 41 , 43 , 45 , 46 , 48 , 50 , 53 , 54 , 56 - 60 . As well as those commonly used techniques, there are some more techniques used for exosome characterization depending on the research purpose before SERS analysis, such as dynamic light scattering 32 , 34 - 36 , 38 , 47 , 60 , zeta potential analyzer 32 , 38 , fluorescence 23 , flow cytometry 43 , 52 , 58 , atomic force microscope 48 , single particle interferometric reflectance imaging sensing 40 , tunable resistive pulse sensing 54 and protein assay kit 60 .…”