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, named AS2-US-AuNP-Aggregate, composed of ultrasmall gold nanoparticles (US-AuNPs) linked by (partially) pairing oligomers that selectively disassemble in the presence of PSA. The system was optimised also using a previously developed in silico routine and is designed for enhanced detection capabilities and for supporting in vivo applicability. We measured the sizes of the nanosystems by dynamic light scattering (DLS) and their extinction spectra, also in the presence of PSA in simple buffers, in the presence of DNaseI, and under blood-mimicking conditions (filtered plasma), obtaining a response down to 10 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 user-friendly diagnostic tools. Additionally, we discuss key optimisation strategies to further advance their development for in vivo diagnostic applications.