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用于灵敏检测替莫唑胺及细胞内成像的自组装聚集诱导发光超分子探针

Self-assembled aggregation-induced emission supramolecular probe for sensitive temozolomide detection and intracellular imaging.

作者信息

Jiang Chenrui, Chen Feifei, Chen Yue, Sun Yu, He Hua, Dramou Pierre, Xu Tao, Xu Hongbin

机构信息

Department of Pharmacy, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, China.

Department of Analytical Chemistry, China Pharmaceutical University, Nanjing, 211198, China.

出版信息

Anal Bioanal Chem. 2025 Aug 14. doi: 10.1007/s00216-025-06045-1.

Abstract

Temozolomide (TMZ) is a first-line chemotherapy drug for treating malignant glioblastoma but faces challenges due to its short plasma half-life and limited brain distribution. There is a need for a more efficient, cost-effective, and sensitive method for monitoring TMZ in clinical settings. This work presents a novel fluorescent probe based on the host-guest interaction of cucurbit[7]uril (CB[7]) and aggregation-induced emission molecule 1,1,2,2-tetra(biphenyl-4-yl)ethene (TTPE) for trace-level detection of TMZ in serum. The CB[7]@TTPE nanoprobe demonstrated high sensitivity, with a detection range of 1-20 μg/mL and a limit of detection of 0.25 μg/mL. Comprehensive characterization by ITC, FT-IR, NMR, UV-vis, and fluorescence spectroscopy confirmed the sensing behavior of the probe. The system exhibited excellent selectivity for TMZ and was successfully applied to serum samples with good recovery rates. In addition, the probe enabled fluorescence imaging of TMZ in human glioma cells (U87 and T98G), making it suitable for monitoring of drug distribution in cellular environments. The self-assembled CB[7]@TTPE probe provides a highly sensitive and selective method for TMZ detection in biological fluids. Its strong fluorescence and water solubility offer promising potential for both clinical diagnostics and drug resistance monitoring in cancer therapy.

摘要

替莫唑胺(TMZ)是治疗恶性胶质母细胞瘤的一线化疗药物,但由于其血浆半衰期短和脑内分布有限而面临挑战。临床上需要一种更高效、经济且灵敏的方法来监测TMZ。这项工作提出了一种基于葫芦[7]脲(CB[7])与聚集诱导发光分子1,1,2,2-四(联苯-4-基)乙烯(TTPE)的主客体相互作用的新型荧光探针,用于血清中痕量水平TMZ的检测。CB[7]@TTPE纳米探针表现出高灵敏度,检测范围为1-20μg/mL,检测限为0.25μg/mL。通过等温滴定量热法、傅里叶变换红外光谱、核磁共振、紫外可见光谱和荧光光谱进行的全面表征证实了该探针的传感行为。该系统对TMZ表现出优异的选择性,并成功应用于血清样品,回收率良好。此外,该探针能够对人胶质瘤细胞(U87和T98G)中的TMZ进行荧光成像,使其适用于监测细胞环境中的药物分布。自组装的CB[7]@TTPE探针为生物流体中TMZ的检测提供了一种高度灵敏且选择性的方法。其强荧光和水溶性为癌症治疗中的临床诊断和耐药性监测提供了有前景的潜力。

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