Study of parameters affecting the assembly of linker-based goldnanoparticle core spherical nucleic acids (AuNP-core SNAs) for colorimetricdetection

Spherical nucleic acids (SNAs) are multivalent nucleic acid structures made up of a layer oftightly packed oligonucleotide shells on the surface of a nanoparticle core. Since the first report ofSNA by Mirkin et al. [۱], there has been great interest in SNAs as they offer new opportunities inthe field of gene and drug delivery. The DNA shell allows specific molecular recognition withmuch higher binding affinity for complementary sequences compared to their linear counterpartswhich can be programmed to recognize and bind DNA targets. Upon binding, aggregation ofAuNP-core SNA red-shifts the surface resonance plasmon (SPR) band, and a visible color changeof the particles in solution from red to purple is observed. The change in the optical property ofgold nanoparticle suspension can be easily monitored with UV-Vis absorption spectroscopy.Colorimetric detection systems based on SNA conjugates have been used for visual detection ofnucleic acids with the naked eye [۲,۳]. In this study, the kinetics of the self-assembly process ofgold nanoparticles modified with phosphorothioate-capped oligonucleotides and complementarylinker strands with palindromic tails were investigated. The engineered mixture of palindromicDNA linkers and SNA resulted in significant time-dependent spectral changes of the AuNPplasmon band due to self-assembly formation in the presence of the DNA linker. Spectral changeswere monitored by tracking the plasmon band of the AuNP core SNA in UV-Vis spectra overtime. A series of experiments and a theoretical model were developed to study the assemblykinetics of SNA using ۲۴ linkers of different lengths and GC content. The kinetics of assemblyformation in linker-based single-component systems was found to depend on the length and GCcontent of the palindromic tail. The result showed that the ۴-nucleotide palindromic linker with۱۰۰% GC content was suitable for colorimetric purposes due to its faster assembly rate and greatercolor change in SNA solutions.