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In this study, nickel nanoparticles (NiONPs) have been successfully synthesized in an aqueous medium using the aqueous extract from the leaves of Calendula officinalis. The synthesized NiONPs were characterized using different techniques. According to the XRD analysis, the mean crystal size for NiONPs was found to be 33.17 nm. In addition, SEM images exhibited a uniform spherical morphology with a size of 60.39 nm for the NiONPs. The anti-esophageal carcinoma potentials of C. officinalis leaf aqueous extract, and NiONPs were assessed by the MTT assay against distal esophageal adenocarcinoma (FLO-1), gastroesophageal junction adenocarcinoma (ESO26), human caucasian esophageal carcinoma (OE33), and human esophageal squamous cell carcinoma (KYSE-270) cell lines. This study showed that NiONPs had excellent cell death and anti-cancer effects against esophageal carcinoma cell lines …