Department of Chemistry, BITS Pilani K K Birla Goa Campus, Zuarinagar, Sancoale 403726, Goa, India.
Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400094, India.
ACS Appl Bio Mater. 2021 Feb 15;4(2):1813-1822. doi: 10.1021/acsabm.0c01527. Epub 2021 Jan 20.
The development of sensitive and selective tools for the detection and quantification of biomarkers is important in the diagnosis and treatment of clinical diseases. Spermine (SP) and spermidine (SPD) act as biomarkers for early-stage diagnosis of cancer in humans as their increased levels in urine are indicative of abnormal biological processes associated with this fatal disease. In this study, we introduced a strategy for solid-supported amplification of the effective aggregation-induced-emission (AIE) effect of a water-soluble tetraphenylethylene (TPE)-based probe in developing a supramolecular sensing platform for the rapid, sensitive, and selective detection of SP and SPD in water. The nonemissive TPE derivative (TPEHP) forms a less emissive conjugate with hydroxyl cucurbit[6]uril (CB[6]OH) in water, which undergoes several-fold enhancement of effective emission upon electrostatic interaction with the solid surface of hydroxyapatite nanoparticles (HAp NPs), dispersed in the aqueous media. The corresponding three-component supramolecular assembly disrupts by the intrusion of SP and SPD in the CB[6] portal because of the stronger binding ability with CB[6], resulting in a turn-off fluorescence sensor for SP and SPD with enhanced sensitivity. The assembly-disassembly-based sensing mechanism was thoroughly demonstrated by carrying out isothermal titration calorimetry (ITC), spectroscopic, and microscopic experiments. The sensing system showed low limits of detection (LODs) of 1.4 × 10 and 3.6 × 10 M for SP and SPD, respectively, which are well below the required range for the early diagnosis of cancer. Besides, a good linear relationship was obtained for both SP and SPD. Nominal interference from various metal ions, anions, common chemicals, amino acids, and other biogenic amines makes this sensing platform suitable for the real-time, low-level measurement of spermine (and spermidine) in human urinary and blood samples.
开发用于检测和定量生物标志物的灵敏和选择性工具对于临床疾病的诊断和治疗非常重要。精胺（SP）和亚精胺（SPD）作为人类癌症早期诊断的生物标志物，其尿液水平升高表明与这种致命疾病相关的异常生物过程。在本研究中，我们引入了一种策略，即在水溶性四苯乙烯（TPE）基探针的有效聚集诱导发射（AIE）效应的固体支持放大，以开发用于快速、灵敏和选择性检测水中 SP 和 SPD 的超分子传感平台。非发光 TPE 衍生物（TPEHP）在水中与羟基葫芦[6]脲（CB[6]OH）形成发光较弱的共轭物，当与分散在水介质中的羟基磷灰石纳米粒子（HAp NPs）的固体表面静电相互作用时，有效发射会增强数倍。相应的三组分超分子组装物由于与 CB[6]更强的结合能力而被 SP 和 SPD 侵入 CB[6]门户所破坏，从而导致 SP 和 SPD 的荧光传感器关闭，灵敏度增强。通过进行等温滴定量热法（ITC）、光谱和显微镜实验，彻底证明了基于组装-解组装的传感机制。该传感系统对 SP 和 SPD 的检测限（LOD）分别低至 1.4×10 和 3.6×10 M，远低于癌症早期诊断所需的范围。此外，还获得了 SP 和 SPD 的良好线性关系。来自各种金属离子、阴离子、常见化学品、氨基酸和其他生物胺的名义干扰使得该传感平台适合于实时、低水平测量人尿和血液样本中的精胺（和亚精胺）。
