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用于癌症诊断的生物响应性微凝胶和多价蛋白结合的白细胞介素-2 和可溶性白细胞介素-2 受体 α 的快速准确检测新工具

New Tool for Rapid and Accurate Detection of Interleukin-2 and Soluble Interleukin-2 Receptor α in Cancer Diagnosis Using a Bioresponsive Microgel and Multivalent Protein Binding.

机构信息

School of Chemical and Biological Engineering, and Institute of Chemical Process, Seoul National University, Seoul 08826, Republic of Korea.

R&D center, Scholar Foxtrot Co. Ltd., Seoul 02841, Republic of Korea.

出版信息

ACS Appl Mater Interfaces. 2021 Jul 28;13(29):33782-33789. doi: 10.1021/acsami.1c04827. Epub 2021 Jul 14.

DOI:10.1021/acsami.1c04827
PMID:34258987
Abstract

Interleukin-2 (IL-2) and its α receptor in soluble form (sIL-2Rα) are considered biomarkers for cancers and immune-related diseases. Enzyme-linked immunosorbent assay is the most common method used to evaluate biomarkers in clinical practice; it is precise but time-consuming and involves complicated procedures. Here, we have developed a rapid yet accurate modality for cancer diagnosis that enables on-site evaluation of cancer markers, that is, IL-2 and sIL-2Rα, without complicated pretreatment of cancer patient-derived blood samples. Surface plasmon resonance and bioresponsive microgels conjugated with IL-2 receptors, that is, IL-2Rβ and IL-2Rγ, were utilized to measure IL-2 and sIL-2Rα levels via multivalent protein binding (MPB) between the ligands and their receptors. Our results showed that this novel method enables us to perform cancer diagnosis with a 1000-fold dilution of serum in 10 min. The advantage of MPB-based cancer diagnosis originates from its great selectivity for a target molecule and tolerance to a myriad of nonspecific substances in serum, which allows on-site clinical evaluation. Importantly, our finding implies that MPB-based cancer diagnosis provides a new paradigm not only for improving cancer treatment but also for evaluating a target molecule in unpurified and complex solutions such as blood.

摘要

白细胞介素-2(IL-2)及其可溶性形式的 α 受体(sIL-2Rα)被认为是癌症和免疫相关疾病的生物标志物。酶联免疫吸附测定是临床实践中评估生物标志物最常用的方法;它精确但耗时且涉及复杂的程序。在这里,我们开发了一种快速而准确的癌症诊断方法,能够现场评估癌症标志物,即 IL-2 和 sIL-2Rα,而无需对癌症患者的血液样本进行复杂的预处理。表面等离子体共振和与 IL-2 受体(即 IL-2Rβ 和 IL-2Rγ)偶联的生物响应性微凝胶被用于通过配体与其受体之间的多价蛋白结合(MPB)来测量 IL-2 和 sIL-2Rα 水平。我们的结果表明,这种新方法使我们能够在 10 分钟内对血清进行 1000 倍稀释以进行癌症诊断。基于 MPB 的癌症诊断的优势源于其对靶分子的高选择性和对血清中无数非特异性物质的耐受性,这允许现场临床评估。重要的是,我们的发现意味着基于 MPB 的癌症诊断不仅为改善癌症治疗提供了新的范例,而且为评估未纯化和复杂溶液(如血液)中的靶分子提供了新的范例。

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