Length-dependent selective killing of brain cancer cells using polyguanine modified gold nanoparticles

Gold nanoparticles (AuNPs) are investigated as a promising therapeutic agent in nanomedicine due to their easy synthesis and surface functionalization. AuNPs also have extraordinary physicochemical properties such as inertness, being plasmonic and biocompatible. AuNPs can be modified using variety of molecules including biological ones, such as deoxyribonucleic acid (DNA), peptides, proteins, carbohydrates for highly exciting applications in various fields of therapeutic nanomedicine such as drug delivery, gene therapy, sensing, detection, and imaging. Among these biological molecules, therapeutic use of oligonucleotides, more specifically guanine-rich (G-rich) oligonucleotides, gain interest due to their anti-proliferative effects in malignant tumor cells. Surface functionalization of AuNPs using G-rich oligonucleotides are being studied in nanomedicine, however, little is known about the cellular response of these hybrid structures as potential therapeutic agents. In this study, we aimed to investigate length-dependent cellular responses of oligonucleotide modified-AuNPs. With this goal in mind, polyadenine-tailed polyguanine sequences (G10 and G20) are used to functionalize the surface of AuNPs. Resulting nanostructures, G10-AuNPs and G20-AuNPs, are used to investigate their effect through cell cycle analysis, apoptosis induction, cellular uptake studies, as well as in vitro cytotoxicity assessments. As a result, increasing number of guanine bases showed enhanced cellular uptake (1.86 fold), increased cell accumulation in S phase (1.67-fold) and G2/M phase (1.34-fold), and elevated induction of apoptosis (two-fold) in glioblastoma (GBM) cells (U87MG and U373) when compared with normal human astrocytes (NHA). In conclusion, the data suggests length-dependent selective killing of GBM cells using polyguanine modified-AuNPs.