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Aptamer/Peptide-Functionalized Nanoprobe for Detecting Multiple miRNAs in Circulating Malignant Cells to Study Tumor Heterogeneity
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2023-09-07 , DOI: 10.1021/acsbiomaterials.3c01055
Di Han 1, 2 , Xiao-He Ren 1 , Xiao-Yan He 3 , Xue-Si Chen 4 , Xuan Pang 4 , Si-Xue Cheng 1
Affiliation  

Identification of diverse biomarkers in heterogenic circulating malignant cells (CMCs) such as circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) has crucial significance in tumor diagnosis. However, it remains a substantial challenge to achieve in situ detection of multiple miRNA markers in living cells in blood. Herein, we demonstrate that an aptamer/peptide-functionalized vector can deliver molecular beacons into targeted living CMCs in peripheral blood of patients for in situ detection of multiple cancer biomarkers, including miRNA-21 (miR-21) and miRNA-221 (miR-221). Based on miR-21 and miR-221 levels, heterogenic CMCs are identified for both nondistant metastatic and distant metastatic cancer patients. CMCs from nondistant metastatic and distant metastatic cancer patients exhibit similar miR-21 levels, while the miR-221 level in CMCs of the distant metastatic cancer patient is higher than that of the nondistant metastatic cancer patient. With the capability to realize precise probing of multiple intracellular biomarkers in living CMCs at the single-cell resolution, the nanoprobe can reveal the tumor heterogeneity and provide useful information for diagnosis and prognosis. The nanoprobe we developed would accelerate the progress toward noninvasive precise cancer diagnosis.

中文翻译:

适体/肽功能化纳米探针用于检测循环恶性肿瘤细胞中的多种 miRNA 以研究肿瘤异质性

异源循环恶性细胞(CMC)如循环肿瘤细胞(CTC)和循环肿瘤内皮细胞(CTEC)中多种生物标志物的鉴定对于肿瘤诊断具有至关重要的意义。然而,实现血液中活细胞中多种 miRNA 标记物的原位检测仍然是一个巨大的挑战。在此,我们证明适体/​​肽功能化载体可以将分子信标递送到患者外周血中的目标活CMC中,用于原位检测多种癌症生物标志物,包括miRNA-21 (miR-21)和miRNA-221 (miR-221)。 221)。根据 miR-21 和 miR-221 水平,鉴定出非远处转移性和远处转移性癌症患者的异源 CMC。非远处转移癌症患者和远处转移癌症患者的 CMC 表现出相似的 miR-21 水平,而远处转移癌症患者 CMC 中的 miR-221 水平高于非远处转移癌症患者。纳米探针能够以单细胞分辨率实现活体CMC中多种细胞内生物标志物的精确探测,可以揭示肿瘤的异质性,为诊断和预后提供有用的信息。我们开发的纳米探针将加速无创精确癌症诊断的进展。
更新日期:2023-09-07
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