Nanocage‐Based Capture‐Detection System for the Clinical Diagnosis of Autoimmune Disease

Abstract

The detection of autoantibodies is critical for diagnosis of autoimmune diseases. However, the sensitivity is often limited by the properties of the antigens and the detection systems such as enzyme‐linked immunosorbent assay (ELISA). Here, employing the multidisplay ability of ferritin, a highly sensitive nanocage‐based capture‐detection system is designed, of which the sensitivity is 100–1000‐fold higher than that of conventional ELISA methods. The capture nanocages are constructed by displaying the primary Sjögren's syndrome (pSS)‐related antigenic peptides on ferritin nanocage, which present epitopes effectively and high affinity, leading to tenfold higher capture capability for autoantibodies. Human IgG Fc‐binding peptides are also engineered on ferritin nanocage, which enable high binding affinity and efficient horseradish peroxidase (HRP)‐labeling. Compared with commercial HRP‐conjugated anti‐human IgG antibody, the nanocage‐based detecting probe exhibited more than tenfold increased sensitivity. Autoantibodies are then examined in 91 sera from patients with pSS, 51 from rheumatoid arthritis, 54 from systemic lupus erythematosus, and 55 from healthy individuals by using the nanocage‐based ELISA. The results indicate that the nanocage‐based capture‐detection system is an effective detection platform and provide a novel and more sensitive method for the diagnosis of autoimmune diseases.

Hemin-Caged Ferritin Acting as a Peroxidase-like Nanozyme for the Selective Detection of Tumor Cells

“…Enzyme-based biosensors have attracted increasing attention because of their wide applications in biomedical researches. , Over the last 2 decades, nanomaterial-based nanozymes, which possess intrinsic enzyme-like ability, have drawn great attention because they can mimic the catalytic activity of natural enzymes. − Nanozymes generally are convenient for large-scale preparation, are highly stable, and have multiple functions. ,, However, it is difficult to control the active sites of nanoparticles to obtain the desired activity for the rational design of nanozymes. , Among various enzymes, peroxidase mimicking is one of the most investigated applications of nanozymes because horseradish peroxidase (HRP) has been widely used in various biomedical assays and biosensing applications, such as immunoassays , and bioelectrodes . Because hemin is the active site of peroxidase, a number of biomimetic nanozymes have been designed by the incorporation of hemin in various materials in order to obtain peroxide-like activity, such as graphene oxide, polymers, carbon nanotubes, metal–organic frameworks, , and synthetic peptides and proteins .…”

Ferritin nanocages: a versatile platform for nanozyme design

“…Based on this, Zhang et al designed a ferritin-based detection probe to improve the sensitivity of autoimmune disease detection. 84 Taking advantage of the multimeric display ability of ferritin, the antigen M3 and a-fodrin was arranged on the surface of ferritin, which greatly enhanced their ability to capture autoantibodies. In a similar manner, they developed a multimeric secondary antibody by displaying a human IgG binding peptide on the surface of ferritin and labeling it with Horseradish Peroxidase (HRP).…”

Ferritin nanocages for early theranostics of tumors via inflammation-enhanced active targeting

“…In this study, human H-ferritin (HFn) was selected as the basic structural motif of the multimodality nanoprobe. Ferritin is a spherical iron storage protein composed of a self-assembled 24-subunit protein shell with an outer diameter of 12 nm and an interior cavity diameter of 8 nm (Fan et al, 2013); it contains multiple active groups that are modifiable in the cavity and external surface (Falvo et al, 2013;He et al, 2019;Jiang et al, 2019a;Jiang et al, 2019b;Li et al, 2012;Uchida et al, 2006;Wang et al, 2021;Zhang et al, 2021). Most importantly, HFn can specifically target tumor cells via an overexpressed tumor biomarker transferrin receptor 1 (TfR1) (Fan et al, 2012;Fan et al, 2018;Fan et al, 2017;Jiang et al, 2020;Li et al, 2010) without additional modifications of extra targeting ligands (Fan et al, 2012;Liang et al, 2014;Zhao et al, 2016).…”