A new light-scattering sensor for screening G-quadruplex stabilizers based on DNA-folding-mediated assembly of gold nanoparticles

In this contribution, we constructed a biosensor for screening G-quadruplex stabilizers based on the assembly of gold nanoparticles functionalized with guanine-rich (G-rich) ssDNA using a light-scattering technique. We synthesized a series of metal-terpyridine complexes and investigated their affinity for quadruplex-DNA using the biosensor. Using the ratio of intensity of the light-scattering peak (I - I-0)/I-0, it can intuitively present the sequence of ability of stabilizing G-quadruplex DNA as follows: complex 1 > complex 3 > MTX > complex 2 > complex 5 > complex 6 > complex 7 > complex 4 > methyl green > TO > complex 8 > cisplatin. As our method allows the quantitative analysis of stabilizer affinity, EC50 values obtained are 4.8, 5.3, 6.1, 6.6, 6.7, 18.2, 20.2, 21.5, 32.2, 41.5 and 48.1 mu M for complex 1, complex 3, MTX, complex 2, complex 5, complex 6, complex 7, complex 4, methyl green, TO and complex 8, respectively. The results have been verified by G-quadruplex fluorescent intercalator displacement (G4-FID) analysis. The proposed approach is a simple, convenient, intuitive and highly sensitive assay for screening G-quadruplex stabilizers. Our developed biosensor provides a promising tool for screening anticancer drugs.