Probing synergistic interplay between bio-inspired peptidomimetic chitosan-copper complexes and doxorubicin

The current investigation reports a novel and facile method for modification of low molecular weight chitosan (Cs) with guanidine moieties, aimed at enhancing its cellular interaction and thus augmenting its cellular internalization. Guadinylated chitosan–copper (Cs-Gn-Cu) chelates, based on copper–nitrogen co-ordination, were established. Characterization of chelates was conducted using 1H NMR, 13C NMR, XPS, XRD, TGA-DTA, and GPC techniques. Anticancer activity of formed chelates was confirmed against A549 cells using MTT assay. Experimental outcomes, for the first time, have provided an empirical evidence for synergistic interaction between the chelated polymer (Cs-Gn-Cu) and the established anti-cancer agent, Doxorubicin (Dox), based on analysis by the Chou Talalay method and estimation of their combination indices. ROS induction was demonstrated as the mechanism of action of the chelated polymer, which supplemented rapid destruction of cancerous cells by Dox. These findings strongly advocate the need for harnessing unexplored potential of these innovative metal polymer chelates in cases of Dox resistant lung cancer, wherein the polymeric system itself would serve as an anti-cancer agent. [Display omitted] •Low molecular weight chitosan was modified with guanidine moieties to function similar to cell penetrating peptides•Novel chelates of guadinylated chitosan based on Copper–Nitrogen co-ordination, were established•Synergistic anticancer activity amongst Doxorubicin and formed complexes was proven using ChouTalalay method in A549 cells•Reactive Oxygenated Species (ROS) induction was identified as primary mechanism of anticancer activity for formed complexes