Lyu Nana, Pedersen Bernadette, Shklovskaya Elena, Rizos Helen, Molloy Mark P, Wang Yuling
ARC Center of Excellence for Nanoscale BioPhotonics and School of Natural Sciences, Faculty of Science and Engineering Macquarie University Sydney New South Wales Australia.
Department of Biomedical Sciences, Faculty of Medicine, Health and Human Sciences Macquarie University Sydney New South Wales Australia.
Exploration (Beijing). 2022 May 9;2(3):20210176. doi: 10.1002/EXP.20210176. eCollection 2022 Jun.
Colorectal cancer (CRC) is the third most diagnosed and the second lethal cancer worldwide. Approximately 30-50% of CRC are driven by mutations in the oncogene, which is a strong negative predictor for response to anti-epidermal growth factor receptor (anti-EGFR) therapy. Examining the phenotype of mutant and wild-type (WT) CRC cells in response to anti-EGFR treatment may provide significant insights into drug response and resistance. Herein, surface-enhanced Raman spectroscopy (SERS) assay was applied to phenotype four cell surface proteins (EpCAM, EGFR, HER2, HER3) in mutant (SW480) and WT (SW48) cells over a 24-day time course of anti-EGFR treatment with cetuximab. Cell phenotypes were obtained using Raman reporter-coated and antibody-conjugated gold nanoparticles (SERS nanotags), where a characteristic Raman spectrum was generated upon single laser excitation, reflecting the presence of the targeted surface marker proteins. Compared to the mutant cells, WT cells were more sensitive to anti-EGFR treatment and displayed a significant decrease in HER2 and HER3 expression. The SERS results were validated with flow cytometry, confirming the SERS assay is promising as an alternative method for multiplexed characterization of cell surface biomarkers using a single laser excitation system.
结直肠癌（CRC）是全球第三大最常被诊断出的癌症，也是第二大致命癌症。大约30%-50%的结直肠癌由癌基因中的突变驱动，这是抗表皮生长因子受体（anti-EGFR）治疗反应的一个强有力的阴性预测指标。研究突变型和野生型（WT）结直肠癌细胞对抗EGFR治疗的反应表型，可能会为药物反应和耐药性提供重要见解。在此，表面增强拉曼光谱（SERS）分析被应用于在使用西妥昔单抗进行抗EGFR治疗的24天时间过程中，对突变型（SW480）和野生型（SW48）细胞中的四种细胞表面蛋白（EpCAM、EGFR、HER2、HER3）进行表型分析。使用涂有拉曼报告分子和偶联抗体的金纳米颗粒（SERS纳米标签）获得细胞表型，其中在单激光激发时产生特征性拉曼光谱，反映靶向表面标记蛋白的存在。与突变型细胞相比，野生型细胞对抗EGFR治疗更敏感，并且HER2和HER3表达显著降低。SERS结果通过流式细胞术得到验证，证实SERS分析作为一种使用单激光激发系统对细胞表面生物标志物进行多重表征的替代方法具有前景。
