Lizoń Anna, Wytrwal-Sarna Magdalena, Gajewska Marta, Drożdż Ryszard
Department of Medical Diagnostics, Faculty of Farmacy, Jagiellonian University Collegium Medicum, Medyczna 9, 30-688 Kraków, Poland.
Academic Centre for Materials and Nanotechnology, University of Science and Technology, 30 Kawiory, 30-055 Kraków, Poland.
Materials (Basel). 2019 Sep 15;12(18):2981. doi: 10.3390/ma12182981.
There is a wide spectrum of malignant diseases that are connected with the clonal proliferation of plasma cells, which cause the production of complete immunoglobulins or their fragments (heavy or light immunoglobulin chains). These proteins may accumulate in tissues, leading to end organ damage. The quantitative determination of immunoglobulin free light chains (FLCs) is considered to be the gold standard in the detection and treatment of multiple myeloma (MM) and amyloid light-chain (AL) amyloidosis. In this study, a silver nanoparticle-based diagnostic tool for the quantitation of FLCs is presented. The optimal test conditions were achieved when a metal nanoparticle (MNP) was covered with 10 particles of an antibody and conjugated by 5-50 protein antigen particles (FLCs). The formation of the second antigen protein corona was accompanied by noticeable changes in the surface plasmon resonance spectra of the silver nanoparticles (AgNPs), which coincided with an increase of the hydrodynamic diameter and increase in the zeta potential, as demonstrated by dynamic light scattering (DLS). A decrease of repulsion forces and the formation of antigen-antibody bridges resulted in the agglutination of AgNPs, as demonstrated by transmission electron microscopy and the direct formation of AgNP aggregates. Antigen-conjugated AgNPs clusters were also found by direct observation using green laser light scattering. The parameters of the specific immunochemical aggregation process consistent with the sizes of AgNPs and the protein particles that coat them were confirmed by four physical methods, yielding complementary data concerning a clinically useful AgNPs aggregation test.
有多种恶性疾病与浆细胞的克隆增殖有关,浆细胞的克隆增殖会导致完整免疫球蛋白或其片段(重链或轻链免疫球蛋白)的产生。这些蛋白质可能在组织中积聚,导致终末器官损伤。免疫球蛋白游离轻链(FLC)的定量测定被认为是多发性骨髓瘤(MM)和淀粉样轻链(AL)淀粉样变性检测和治疗的金标准。在本研究中,提出了一种基于银纳米颗粒的FLC定量诊断工具。当金属纳米颗粒(MNP)被10个抗体颗粒覆盖并与5 - 50个蛋白质抗原颗粒(FLC)偶联时,可实现最佳测试条件。如动态光散射(DLS)所示,第二抗原蛋白冠的形成伴随着银纳米颗粒(AgNP)表面等离子体共振光谱的显著变化,这与流体动力学直径的增加和zeta电位的增加相一致。如透射电子显微镜和AgNP聚集体的直接形成所示,排斥力的降低和抗原 - 抗体桥的形成导致了AgNP的凝集。通过绿色激光散射直接观察也发现了抗原偶联的AgNP簇。通过四种物理方法证实了与AgNP及其包被的蛋白质颗粒大小一致的特异性免疫化学聚集过程的参数,产生了关于临床上有用的AgNP聚集试验的补充数据。