Abstract:
Breast cancer (BC) is a major global health problem, with ≈20-25% of patients overexpressing human epidermal growth factor receptor 2 (HER2), an aggressive marker, yet access to early detection and treatment varies across countries. A low-cost, equipment-free, and easy-to-use polydiacetylene (PDA)-based colorimetric sensor is developed for HER2-overexpressing cancer detection, designed for use in low- and middle-income countries (LMICs). PDA nanoparticles are first prepared through thin-film hydration. Subsequently, hydrophilic magnetic nanoparticles and HER2 antibodies are sequentially conjugated to them. The synthesized HER2-MPDA can be concentrated and separated by a magnetic field while inheriting the optical characteristics of PDA. The specific binding of HER2 antibody in HER2-MPDA to HER2 receptor in HER2-overexpressing exosomes causes a blue-to-red color change by altering the molecular structure of the PDA backbone. This colorimetric sensor can simultaneously separate and detect HER2-overexpressing exosomes. HER2-MPDA can detect HER2-overexpressing exosomes in the culture medium of HER2-overexpressing BC cells and in mouse urine samples from a HER2-overexpressing BC mouse model. It can selectively isolate and detect only HER2-overexpressing exosomes through magnetic separation, and its detection limit is found to be 8.5 × 108 particles mL-1. This colorimetric sensor can be used for point-of-care diagnosis of HER2-overexpressing BC in LMICs.
摘要:
乳腺癌(BC)是一个重大的全球性健康问题,人类表皮生长因子受体2(HER2)过度表达的患者约20-25%,一个侵略性的标记,然而,各国获得早期检测和治疗的机会各不相同。低成本,无设备,和易于使用的基于聚二乙炔(PDA)的比色传感器被开发用于HER2过度表达的癌症检测,设计用于低收入和中等收入国家(LMICs)。首先通过薄膜水合制备PDA纳米颗粒。随后,亲水性磁性纳米颗粒和HER2抗体依次与它们缀合。合成的HER2-MPDA可以通过磁场浓缩和分离,同时继承PDA的光学特性。HER2-MPDA中的HER2抗体与过表达HER2的外泌体中的HER2受体的特异性结合通过改变PDA主链的分子结构而引起蓝色到红色的变化。这种比色传感器可以同时分离和检测HER2过表达的外泌体。HER2-MPDA可以在HER2过表达的BC细胞的培养基中和来自HER2过表达的BC小鼠模型的小鼠尿液样品中检测HER2过表达的外泌体。它可以通过磁性分离选择性地分离和检测仅HER2过表达的外泌体,检测限为8.5×108颗粒mL-1。该比色传感器可用于LMIC中HER2过表达BC的即时诊断。