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的挑战。通常需要监测多种生物标志物。在这项研究中,我们开发了一种新的基于聚集诱导发射(AIE)的双功能策略,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存在的情况下,它特异性结合到探针的PSA特异性传感位点，导致荧光信号的恢复，使PSA的线性传感。对于PSMA的检测，在探针上修饰的PSMA靶向配体可以特异性识别PSMA，诱导AIE材料的聚集并导致增强的荧光信号。此外，开发了一种基于脂质体的人造细胞来模拟真正的前列腺癌细胞，并用于研究监测这两种抗原的可行性。利用这种双功能荧光策略，我们对PSA的游离血清抗原生物标志物和PSMA的原位膜抗原进行了双重分析.该测定显示PSA检测的线性范围从0.0001到0.1μg/mL，低检测限（LOD）为6.18pg/mL。对于PSMA，获得的LOD为8.79pg/mL，线性范围为0.0001～0.1μg/mL。这种策略使我们能够同时评估两种生物标志物在活的人类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高度准确和选择性的工具。
