Self-assembled nanoparticles composed of glycol chitosan-dequalinium for mitochondria-targeted drug delivery

Cancer cells divide uncontrollably due to their metabolic imbalance, resistance to mitochondria-mediated apoptosis, and ability to sustain telomere crisis by activating telomere reverse transcriptase. Therefore, mitochondria-mediated cell death has gained considerable attention as an alternative strategy to kill cancer cells. In the present study, an amphiphilic polymer composed of glycol chitosan (GC) and dequalinium (DQA), was synthesized via Michael addition reaction using a methyl acrylate linker and used to target mitochondria. DQA was selected as the mitochondria targeting moiety as well as the lipophilic component of polymer that will self-assemble into nanoparticles in aqueous solvent. GC-DQA nanoparticles were nontoxic compared to positive control when cell viability were assessed in both cancerous and non-cancerous cells. Mitochondria targeting and cell uptake was confirmed by confocal microscopy and flow cytometry, respectively. Curcumin was selected as the anticancer drug and while tested in vitro, the IC₅₀ concentration of the micellar form was 10 μM in cancer cells. These results validate the promising potential of GC-DQA nanoparticles as an efficient mitochondria-targeting drug delivery system for cancer therapy.