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.

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(T ₂ G ₄ ) 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(T ₂ AG ₃ ) ₃ [HUM-12] and d(T ₂ AG ₃ ) ₄ T [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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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