Compartmentalized bimetal cluster-poly(aniline) hybrid nanostructures for multiplexed detection of autoantibodies in early diagnosis of rheumatoid arthritis

Abstract

Multi-compartmentalized, inorganic-organic hybrid nanostructures have been studied in biomedical applications due to their compositional and structural differences in each compartment. The combination of these hybrid nanostructures with metallic nanoparticle clusters would be attractive due to their interparticle plasmonic coupling for photonics-based biosensing. We herein report a new class of compartmentalized bimetal clusterpoly(aniline) hybrid nanostructures (CBCPHNs) for surface-enhanced Raman scattering (SERS)-based, multiplexed detection of autoantibodies in early diagnosis of rheumatoid arthritis (RA). The bimetallic nanoparticle clusters (BNCs) were prepared in a core-shell form by Raman dye-induced aggregation of gold nanoparticles (GNPs) for the core and reduction of silver ions onto GNP nanoclusters for the shell. Subsequently, CBCPHNs were formed by one-directional growth of poly(aniline) via surface-templated polymerization of aniline monomers as well as additional Ag deposition onto BNCs in the presence of a surfactant. The CBCPHNs showed significant electromagnetic field enhancement at both GNP aggregates and Au core-Ag shell gaps of the BNCs, whereas the poly(aniline) counter-compartment served as a biomolecular conjugation site. In addition, we developed a sandwich-type immunoassay platform using these hybrid nanostructures as SERS nanoprobes and magnetic beads (MBs) for early diagnosis of RA in multiplexing. Autoantibodies against cyclic citrullinated peptide (anti-CCP) and rheumatoid factor immunoglobulin M (RF IgM) were simultaneously detected, and quantified measuring SERS signals of sandwich-type immunocomplexes. Multiplexing of anti-CCP and RF IgM was achieved in low concentration ranges, and their limits of detection were 0.68 IU/mL and 0.93 IU/mL, respectively. These hybrid nanostructures with collective functionalities represent potential nanomaterials for multiplexed detection of autoantibodies.