Accurate quantification of proprotein convertase subtilisin/kexin
type 9 (PCSK9) in serum before and after the medication is helpful
in grasping the evolution of PCSK9-related disease and evaluating
the efficacy of PCSK9 inhibitors. Conventional approaches for PCSK9
quantification suffered from complicated operations and low sensitivity.
By integrating stimuli-responsive mesoporous silica nanoparticles,
dual-recognition proximity hybridization, and T7 exonuclease-assisted
recycling amplification, a novel homogeneous chemiluminescence (CL)
imaging approach was proposed for ultrasensitive and convenient immunoassay
of PCSK9. Owing to the intelligent design and signal amplification
property, the whole assay was conducted without separation and rinsing,
significantly simplifying the procedure and eliminating the errors
associated with the professional operation; meanwhile, it showed linear
ranges over 5 orders of magnitude and detection limit as low as 0.7
pg mL–1. Parallel testing was allowed due to the
imaging readout, which brought a maximum throughput of 26 tests h–1. The proposed CL approach was applied to analyze
PCSK9 from hyperlipidemia mice before and after the intervention of
the PCSK9 inhibitor. Serum PCSK9 levels in the model group and the
intervention group could be distinguished efficiently. The results
were reliable compared to commercial immunoassay results and histopathologic
findings. Thus, it could facilitate the monitoring of the serum PCSK9
level and the lipid-lowering effect of the PCSK9 inhibitor, showing
promising potential in bioanalysis and pharmaceuticals.