黑色素瘤仍然是皮肤癌死亡的主要原因。尽管靶向治疗取得了进步，但患者经常产生耐药性，导致疾病在一年内恶化。这种抵抗可能是由于黑色素瘤细胞的上皮间质转化（EMT）样表型转换所致。追踪细胞外囊泡 (EV) 上与 EMT 相关的表型变化有可能尽早了解对靶向治疗的反应和黑色素瘤进展。然而，关于参与 EMT 样过程的黑色素瘤 EV 携带的蛋白质生物标志物的知识仍有待探索。在此，我们提出了一种集成表面增强拉曼散射和交流电流电流体动力学诱导的纳米混合增强的生物传感器，用于在靶向治疗期间灵敏检测 EV 表面上的 EMT 相关生物标志物。该生物传感器成功追踪经丝裂原激活蛋白激酶抑制剂 (MAPKi) 处理的黑色素瘤细胞系中类似 EMT 的表型转换。通过对接受 MAPKi 治疗并产生耐药性的患者进行纵向监测，我们的生物传感器显示出其识别循环 EV 上类似 EMT 的表型转换的能力。这种能力可能可用于预测靶向治疗耐药性的发展，从而实现及时干预和个性化治疗策略。版权所有 © 2023 作者。由 Elsevier B.V. 出版。保留所有权利。

Melanoma continues to be a leading cause of mortality among skin cancers. Despite advancements in targeted therapy, patients frequently develop resistance, leading to disease progression within a year. This resistance may result from the epithelial-to-mesenchymal transition (EMT)-like phenotype switching of melanoma cells. Tracking EMT-related phenotypic changes on extracellular vesicles (EVs) has potential to inform early about response to targeted therapy and melanoma progression. However, the knowledge on protein biomarkers carried by melanoma EVs involved in the EMT-like process remains unexplored. Herein, we present a biosensor integrating surface-enhanced Raman scattering and alternating current electrohydrodynamics-induced nanomixing enhancement, for sensitive detection of EMT-associated biomarkers on EV surfaces during targeted therapy. This biosensor successfully tracks the EMT-like phenotype switching in melanoma cell lines treated with mitogen-activated protein kinase inhibitor (MAPKi). Longitudinal monitoring of patients who receive MAPKi therapy and develop resistance, our biosensor shows its ability to identify the EMT-like phenotype switching on circulating EVs. This ability potentially can be leveraged to predict the development of resistance to targeted therapy, allowing for timely intervention and personalized treatment strategies.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.