Green-synthesized silver nanoparticles from Syzygium aromaticum extract promote cancer cell death by targeting redox and inflammatory pathways

Clove ( Syzygium aromaticum ) is a medicinal spice rich in bioactive compounds with potent antioxidant and therapeutic activities, making it a promising candidate for anticancer applications. Leveraging these properties, we synthesized green silver nanoparticles loaded with S. aromaticum extract (AgNPs-SAE) to enhance its antitumor potential. This study evaluated the efficacy of SAE and AgNPs-SAE in Ehrlich solid tumor (EST)-bearing mice, compared with doxorubicin (DOX). Forty mice were divided into four groups ( n = 10): untreated EST control, SAE (500 mg/kg, orally), AgNPs-SAE (30 mg/kg, orally), and DOX (10 mg/kg, i. p., for 3 days). In vitro , SAE and AgNPs-SAE exhibited cytotoxicity against NBL and MCF7 cells, with higher potency observed for AgNPs-SAE. In vivo , both SAE and AgNPs-SAE significantly reduced tumor growth, with tumor volumes decreased, compared to the untreated group, and extended survival compared to the untreated and DOX-treated groups. Unlike DOX, which elevated hepatic and renal biomarkers in the mouse model, SAE and AgNPs-SAE preserved organ function. These findings indicate that, in this preclinical study, SAE and AgNPs-SAE exhibit promising antitumor efficacy with reduced hepatorenal toxicity compared to DOX, supporting further investigation in preclinical models. Mechanistic analyses indicated that SAE and AgNPs-SAE exerted antitumor effects by reducing oxidative stress and inflammation, promoting apoptotic cell death, and inhibiting tumor cell proliferation, suggesting a multi-targeted mechanism of action. In conclusion, SAE and AgNPs-SAE demonstrate promising antitumor potential with fewer side effects than conventional chemotherapeutics like DOX. The enhanced efficacy of AgNPs-SAE underscores the advantage of combining phytochemicals with nanotechnology to develop safer and more effective cancer therapies.