PSA-Responsive Aptamer-Based Switchable Aggregates of Ultrasmall Gold Nanoparticles

Prostate-specific antigen (PSA) is a key biomarker for the early detection of prostate cancer recurrence following surgical treatment. In this study, we present a PSA-responsive, aptamer-based switchable aggregate system (AS2-US-AuNPs-Aggregate) composed of ultrasmall gold nanoparticles (US-AuNPs) linked by (partially) pairing oligomers that selectively disassemble in the presence of PSMA. The system was optimized also using a previously developed in-silico routine, and is designed for enhanced sensing capabilities and for supporting in vivo applica-bility. We measured the sizes of the nanosystems by dynamic light scattering (DLS), and their extinction spectra, also in presence of PSA in simple buffers, in the presence of DNAse, and under blood-mimicking conditions (filtered plasma) and We measured a response down to 1 fM PSA in buffers and to 1 pM in filtered plasma. Our findings highlight the potential of aptamer-based nanoparticle aggregates as a basis for us-er-friendly, portable diagnostic tools. Additionally, we discuss key optimization strat-egies to further advance their development for in-vivo diagnostic applications.