Targeted delivery of Zingiber officinale Roscoe extract-loaded chitosan nanoparticles for inhibition of multidrug-resistant Escherichia coli-induced HCT-116 colon cancer

Abstract The emergence of multidrug-resistant ( MDR ) Escherichia coli ( E. coli ) is a growing concern, as it significantly contributes to colon cancer initiation and progression. Conventional treatment strategies face challenges such as poor bioavailability and antibiotic resistance, necessitating the development of targeted therapies. This study evaluates the efficacy of Zingiber officinale Roscoe (ginger) extract-loaded chitosan nanoparticles ( GELCs ) in inhibiting MDR E. coli -induced colon cancer using the HCT-116 cell line. The nanoparticles were synthesized with an average size of 150 ± 5 nm, a zeta potential of + 32.5 mV, and an encapsulation efficiency of 84.3%. Their biological activity was assessed through in vitro and in vivo models, focusing on antimicrobial effects, cytotoxicity, apoptosis induction, and inflammatory modulation. The GELCs exhibited potent antimicrobial activity, reducing MDR E. coli colony-forming units (CFUs) by 83% compared to untreated co-cultures. MTT assay results showed a dose-dependent reduction in HCT-116 cell viability, with an IC₅₀ of 22.8 µg/mL , which was significantly lower than that of free ginger extract (IC₅₀ = 48.6 µg/mL), indicating enhanced efficacy. Flow cytometry analysis confirmed increased apoptosis, with a BAX/BCl-2 ratio of 11.3 in the GELC -treated group compared to 1.0 in the control . ELISA assays further demonstrated a reduction in inflammatory cytokines, with IL-6, TNF-α, and IL-1β levels decreasing by 54%, 61%, and 47% , respectively. These findings highlight the dual antimicrobial and anticancer potential of GELCs , making them a promising candidate for targeted therapy against MDR E. coli -associated colon cancer. This study underscores the advantages of nanoparticle-based delivery systems in enhancing the therapeutic efficacy of natural bioactive compounds.