Studying the Interaction between Bendamustine and DNA Molecule with SERS Based on AuNPs/ZnCl2/NpAA Solid-State Substrate

Bendamustine (BENDA) is a bifunctional alkylating agent with alkylating and purinergic antitumor activity, which exerts its anticancer effects by direct binding to DNA, but the detailed mechanism of BENDA-DNA interaction is poorly understood. In this paper, the interaction properties of the anticancer drug BENDA with calf thymus DNA (ctDNA) were systematically investigated based on surface-enhanced Raman spectroscopy (SERS) technique mainly using a novel homemade AuNPs/ZnCl2/NpAA (NpAA: nano porous anodic alumina) solid-state substrate and combined with ultraviolet-visible spectroscopy and molecular docking simulation to reveal the mechanism of their interactions. We experimentally compared and studied the SERS spectra of ctDNA, BENDA, and BENDA-ctDNA complexes with different molar concentrations (1:1, 2:1, 3:1), and summarized their important characteristic peak positions, their peak position differences, and hyperchromic/hypochromic effects. The results showed that the binding modes include covalent binding and hydrogen bonding, and the binding site of BENDA to DNA molecules is mainly the N7 atom of G base. The results of this study help to understand and elucidate the mechanism of BENDA at the single-molecule level, and provide guidance for the further development of effective new drugs with low toxicity and side effects.

Automated summary

In this study, the interaction properties of the anticancer drug BENDA with ctDNA were investigated using surface-enhanced Raman spectroscopy, UV-visible spectroscopy, and molecular docking simulation. The results showed that BENDA binds to ctDNA through covalent binding and hydrogen bonding, with the N7 atom of G base as the main binding site. This study helps to understand the mechanism of BENDA at the single-molecule level and provides guidance for the development of effective new drugs with low toxicity and side effects.