关键词: EMPAS actin antifouling linker atomic force microscopy chemiluminescence gelsolin lysophosphatidic acid nanoparticles ovarian cancer

Mesh : Lysophospholipids Humans Female Ovarian Neoplasms / diagnosis Biomarkers, Tumor Biosensing Techniques Gelsolin Actins Early Detection of Cancer

来  源:   DOI:10.3390/bios14060287   PDF(Pubmed)

Abstract:
The overall 5-year survival rate of ovarian cancer (OC) is generally low as the disease is often diagnosed at an advanced stage of progression. To save lives, OC must be identified in its early stages when treatment is most effective. Early-stage OC causes the upregulation of lysophosphatidic acid (LPA), making the molecule a promising biomarker for early-stage detection. An LPA assay can additionally stage the disease since LPA levels increase with OC progression. This work presents two methods that demonstrate the prospective application for detecting LPA: the electromagnetic piezoelectric acoustic sensor (EMPAS) and a chemiluminescence-based iron oxide nanoparticle (IONP) approach. Both methods incorporate the protein complex gelsolin-actin, which enables testing for detection of the biomarker as the binding of LPA to the complex results in the separation of gelsolin from actin. The EMPAS was characterized with contact angle goniometry and atomic force microscopy, while gelsolin-actin-functionalized IONPs were characterized with transmission electron microscopy and Fourier transform infrared spectroscopy. In addition to characterization, LPA detection was demonstrated as a proof-of-concept in Milli-Q water, buffer, or human serum, highlighting various LPA assays that can be developed for the early-stage detection of OC.
摘要:
卵巢癌(OC)的总体5年生存率通常较低,因为该疾病通常在进展的晚期被诊断。为了拯救生命,必须在治疗最有效的早期阶段确定OC。早期OC引起溶血磷脂酸(LPA)的上调,使分子成为早期检测的有希望的生物标志物。由于LPA水平随OC进展而增加,因此LPA测定可以额外地对疾病进行分期。这项工作提出了两种方法,证明了检测LPA的前瞻性应用:电磁压电声传感器(EMPAS)和基于化学发光的氧化铁纳米颗粒(IONP)方法。两种方法都包含蛋白质复合物凝溶胶蛋白-肌动蛋白,这使得能够测试生物标志物的检测,因为LPA与复合物的结合导致凝溶胶蛋白与肌动蛋白的分离。用接触角测角法和原子力显微镜对EMPAS进行了表征,而凝溶胶蛋白-肌动蛋白功能化的IONP用透射电子显微镜和傅里叶变换红外光谱进行了表征。除了表征,LPA检测在Milli-Q水中被证明是一种概念验证,缓冲区,或者人类血清,突出了可以开发用于早期检测OC的各种LPA测定法。
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