DNA Nanocage-Assisted Size-Selective Recognition and Quantification toward Low-Mass Soluble ß-Amyloid Oligomers.

ABSTRACT

Low-mass soluble ß-amyloid peptide oligomers (LSAßOs) play a crucial role in the pathogenesis of Alzheimer's disease. However, these oligomers exhibit heterogeneity in terms of structure, stability, and stoichiometry, and their abundance in biofluids is low, making accurate identification challenging. In this study, we developed a DNA nanocage-assisted method for selective sizing and sensitive quantification of LSAßOs in serum. Using LSAßO less than 10 kDa (LSAßO10kD) and less than 30 kDa (LSAßO30kD) as models, the size-matching rules between DNA nanocages and LSAßOs were investigated, and two appropriate nanocages were selected for the detection of two LSAßOs, respectively. Both nanocages were functionalized by encapsulating oligomer's aptamer and a complementary sequence within their cavities. Once the LSAßO entered the corresponding nanocage cavity, the complementary sequence was released, triggering a hybridization chain reaction on an electrochemical sensing platform. The system achieved size-selective discrimination of LSAßO10kD with a linear range of 10-150 pM and LSAßO30kD with a linear range of 15-150 pM. Real sample testing confirmed the applicability of the method for blood-based diagnosis. The DNA nanocage-assisted electrochemical analysis platform provides an accurate, highly selective, and sensitive approach for oligomer analysis, which is significant for amyloid protein research and related disease diagnosis.