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构建一种用于肿瘤进展期间过氧亚硝酸盐的比率型荧光探针。

Construction of a near-infrared fluorescent probe for ratiometric imaging of peroxynitrite during tumor progression.

机构信息

Key Laboratory of Life-Organic Analysis of Shandong Province, School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, P.R. China.

出版信息

Analyst. 2021 Aug 9;146(16):5204-5211. doi: 10.1039/d1an00980j.

Abstract

Malignant tumors are one of the main causes for human death and are tightly associated with overexpression of reactive oxygen species (ROS) in pathological processes. Therefore, in vivo monitoring of ROS, especially ONOO-, remains of great significance for diagnosis and therapy of tumors to improve the survival rate. Herein, we designed and constructed a reliable near-infrared (NIR) ratiometric fluorescent biosensor CDMS for monitoring the fluctuations of ONOO- in the process of tumor progression. CDMS featured outstanding stability to photoirradiation, substantial quantum yields, rapid response (<5 s), high selectivity and excellent biocompatibility. Moreover, CDMS exhibited distinct ratiometric fluorescence signal changes after reacting with ONOO-. Fluorescence imaging in immune stimulated cells indicated that CDMS was competent to determine the levels of ONOO- in the cellular level. Remarkably, CDMS was further applied in monitoring the expression of ONOO- in a peritonitis mouse model and tumor-bearing mouse model. Based on the excellent properties of CDMS, the probe exhibited the potential for noninvasive in vivo visualization of ONOO- in the occurrence and process of tumor development. It is envisioned that CDMS can be employed as a promising tool for monitoring the ONOO- fluxes in tumor pathological progression, especially for tumor diagnosis and therapy.

摘要

恶性肿瘤是人类死亡的主要原因之一,与病理过程中活性氧物种 (ROS) 的过度表达密切相关。因此,体内监测 ROS,特别是过氧亚硝酸盐 (ONOO-),对于提高肿瘤的诊断和治疗的生存率仍然具有重要意义。在此,我们设计并构建了一种可靠的近红外 (NIR) 比率荧光生物传感器 CDMS,用于监测肿瘤进展过程中 ONOO-的波动。CDMS 具有出色的抗光照射稳定性、高量子产率、快速响应(<5s)、高选择性和良好的生物相容性。此外,CDMS 在与 ONOO-反应后表现出明显的比率荧光信号变化。在免疫刺激细胞中的荧光成像表明,CDMS 能够在细胞水平上测定 ONOO-的水平。值得注意的是,CDMS 进一步应用于监测腹膜炎小鼠模型和荷瘤小鼠模型中 ONOO-的表达。基于 CDMS 的优异性能,该探针有望成为非侵入性体内可视化肿瘤发展过程中 ONOO-的潜在工具。可以预见,CDMS 可以作为监测肿瘤病理进展中 ONOO-通量的一种有前途的工具,特别是用于肿瘤的诊断和治疗。

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