Prospecting the cancer therapeutic edge of chitosan-based gold nanoparticles through conformation selective binding to the parallel G-quadruplex formed by short telomeric DNA sequence: A multi-spectroscopic approach

Abstract

The biological relevance of G4 structures formed in telomere & oncogenes promoters make them extremely crucial therapeutic target for cancer treatment. Herein, we have synthesized chitosan-based gold nanoparticles (CH-Au NPs) through green method and have investigated their interaction with G4 structures formed by short telomeric sequences to evaluate their potential for targeting G4 structures. Firstly, we have characterized morphological/physical attributes of synthesized CH-Au NPs and salt dependent structural aspects of model G-rich DNA sequence, 12-mer d(T2G4)2 [TETRA] using spectroscopic and biophysical techniques. The molecular interactions between CH-Au NPs and parallel/antiparallel TETRA G4 structures were evaluated using UV–Visible, CD, Fluorescence, CD melting, DLS and Zeta potential studies. The experimental data indicated that CH-Au NPs showed strong binding interactions with Parallel TETRA G4 and provided thermal stabilization to the structure, whereas their interactions with Antiparallel TETRA G4 DNA and Ct-DNA (DNA duplex) were found to be negligible. Further, CH-Au NPs were also investigated for their selectivity aptitude for different G4 structures formed by human telomeric sequences; d(T2AG3)3 [HUM-12] and d(T2AG3)4T [HUM-25]. Our findings suggested that CH-Au NPs exhibited topology specific binding aptitude towards G4 structure, which can be utilized to inhibit/modulate crucial biological functions for potential anticancer activity.