Yin Mengai, Wang Tong, Wang Zhijie, Lu Lina, Ding Bowen, Chi Jiadong, Wang Xiangrui, Xue Lan, Dai Fuju, Hu Bingxin, Jiao Jun, Chen Qiang
The Key Laboratory of Bioactive Materials Ministry of Education, College of Life Science, Nankai University, Weijin Road No.94, Tianjin, 300071, PR China.
Department of Breast Oncoplastic and Reconstructive Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, 300060, PR China.
Biosens Bioelectron. 2025 Nov 15;288:117813. doi: 10.1016/j.bios.2025.117813. Epub 2025 Jul 22.
With its high porosity and tunable properties, metal-organic frameworks (MOFs) serve as nano-cornucopias, unlocking limitless possibilities in biosensing applications. Herein, we designed an ultrasensitive biosensor leveraging MOFs as a multifunctional nano-platform to implement a synergistic self-calibration strategy for the ultra-accurate quantification of breast cancer-related human epidermal growth factor receptor-2 (HER-2). This approach integrates (1) ratiometric electrochemistry for built-in correction to minimize non-specific interference and (2) dual-modal electrochemical and colorimetric detection for enhanced accuracy through cross-validation. Functionalized NH-UiO-66 (Zr-MOF) was employed as a carrier to incorporate a dual-layer of anthraquinone-2-carboxylic acid (AQ), creating NH-UiO-66@AQ, a highly electroactive nanomaterial for signal amplification. The incorporation of gold nanoparticles (AuNPs) and ionically reduced graphene oxide (IL-rGO) further enhanced conductivity and electrochemical response. Additionally, MOF@FeTCPP nanozyme was synthesized by encapsulating iron (III) meso-tetra(4-carboxyphenyl) porphyrin chloride (FeTCPP) into HKUST-1 (Cu-MOF), demonstrating exceptional peroxidase-like activity. Coupling this nanozyme with streptavidin (SA) resulted in the formation of a dual-signal nanozyme probe (DSN-Probe) capable of generating both electrochemical and colorimetric signals. The biosensor exhibited a broad detection range (100 fg/mL to 150 ng/mL) with an ultra-low limit of detection (LOD) of 28.509 fg/mL, effectively differentiating HER-2 expression in various cell lines and distinguishing HER-2 levels in serum samples from healthy individuals and breast cancer patients. Its adaptability to electrochemical workstations, microplate readers, and smartphones makes it ideal for point-of-care testing (POCT), reinforcing its potential as a powerful tool for drug mechanism studies and breast cancer diagnosis.
金属有机框架材料（MOFs）具有高孔隙率和可调节的性质，犹如纳米聚宝盆，为生物传感应用开启了无限可能。在此，我们设计了一种超灵敏生物传感器，利用MOFs作为多功能纳米平台，实施协同自校准策略，以实现对乳腺癌相关的人表皮生长因子受体2（HER-2）的超精确量化。该方法整合了：（1）用于内置校正以最小化非特异性干扰的比率电化学；以及（2）用于通过交叉验证提高准确性的双模式电化学和比色检测。功能化的NH-UiO-66（Zr-MOF）用作载体，结合了蒽醌-2-羧酸（AQ）双层，形成了NH-UiO-66@AQ，一种用于信号放大的高电活性纳米材料。金纳米颗粒（AuNPs）和离子还原氧化石墨烯（IL-rGO）的加入进一步提高了导电性和电化学响应。此外，通过将氯化铁（III）中四（4-羧基苯基）卟啉（FeTCPP）封装到HKUST-1（Cu-MOF）中合成了MOF@FeTCPP纳米酶，其表现出优异的过氧化物酶样活性。将这种纳米酶与链霉亲和素（SA）偶联，形成了一种能够产生电化学和比色信号的双信号纳米酶探针（DSN-探针）。该生物传感器具有宽检测范围（100 fg/mL至150 ng/mL），超低检测限（LOD）为(28.509 fg/mL)，能有效区分各种细胞系中的HER-2表达，并区分健康个体和乳腺癌患者血清样本中的HER-2水平。它对电化学工作站、微孔板读数器和智能手机的适应性使其非常适合即时检测（POCT），增强了其作为药物机制研究和乳腺癌诊断有力工具的潜力。
