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通过基于聚集诱导发射的双功能探针同时靶向和监测前列腺癌细胞中的游离抗原和原位膜抗原。

Simultaneous targeting and monitoring of free antigen and in-situ membrane antigen in prostate cancer cells via an aggregation-induced emission-based bifunctional probe.

机构信息

School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, 212003, Jiangsu Province, PR China.

Affiliated Hospital of Jiangsu University, Zhenjiang, 212001, Jiangsu Province, PR China.

出版信息

Biosens Bioelectron. 2024 Nov 1;263:116581. doi: 10.1016/j.bios.2024.116581. Epub 2024 Jul 26.

DOI:10.1016/j.bios.2024.116581
PMID:39079208
Abstract

The precise clinical diagnosis of prostate cancer still presents inherent challenges, and usually a monitoring of multiple biomarkers is required. In this study, a new aggregation-induced emission (AIE)-based bifunctional strategy was developed for the simultaneous detection of prostate cancer-specific in situ membrane antigens (PSMA) and free antigens (PSA). First, a bifunctional fluorescent probe with double sensing sites (a PSA-specific sensing site and a PSMA-targeted ligand) was constructed. In the presence of PSA, it specifically binds to the PSA-specific sensing site of the probe, resulting in the restoration of the fluorescence signal, enabling linear sensing of PSA. For the detection of PSMA, the PSMA-targeted ligand modified on the probe can specifically recognize PSMA, inducing the aggregation of the AIE material and resulting in an enhanced fluorescence signal. Moreover, a liposome-based artificial cell was developed to simulate the real prostate cancer cell, and it was used to investigate the feasibility of monitoring the two types of antigens. Utilizing this bifunctional fluorescent strategy, a dual-analysis of free serum antigen biomarker of PSA and in-situ membrane antigen of PSMA was achieved. The assay exhibited a wide linearity range for PSA detection from 0.0001 to 0.1 μg/mL, with a low limit of detection (LOD) of 6.18 pg/mL. For PSMA, the obtained LOD is 8.79 pg/mL, with a linearity range from 0.0001 to 0.1 μg/mL. This strategy allows us to simultaneously assess the levels of two types of biomarkers in living human prostatic cancer cells, providing a highly accurate and selective tool for early screening and monitoring of prostatic cancer.

摘要

前列腺癌的精确临床诊断仍然存在固有挑战,通常需要监测多种生物标志物。在本研究中,开发了一种新的聚集诱导发射(AIE)双功能策略,用于同时检测前列腺癌特异性原位膜抗原(PSMA)和游离抗原(PSA)。首先,构建了一种具有双传感位点(PSA 特异性传感位点和 PSMA 靶向配体)的双功能荧光探针。在 PSA 存在下,它特异性地与探针的 PSA 特异性传感位点结合,导致荧光信号恢复,从而能够对 PSA 进行线性传感。对于 PSMA 的检测,探针上修饰的 PSMA 靶向配体可以特异性识别 PSMA,诱导 AIE 材料的聚集,从而产生增强的荧光信号。此外,还开发了一种基于脂质体的人工细胞来模拟真实的前列腺癌细胞,并用于研究监测两种类型抗原的可行性。利用这种双功能荧光策略,实现了对游离血清抗原生物标志物 PSA 和原位膜抗原 PSMA 的双重分析。该测定法对 PSA 的检测具有从 0.0001 至 0.1μg/mL 的宽线性范围,检测限(LOD)低至 6.18pg/mL。对于 PSMA,获得的 LOD 为 8.79pg/mL,线性范围从 0.0001 至 0.1μg/mL。该策略允许我们同时评估两种类型生物标志物在活的人前列腺癌细胞中的水平,为前列腺癌的早期筛查和监测提供了一种高度准确和选择性的工具。

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