Cytotoxicity of Green Synthesized Silver Nanoparticles Against Oral Cell Lines: A Systematic Review and Meta-Analysis

This systematic review aimed to evaluate the cytotoxic effects of green-synthesized silver nanoparticles (GS-AgNPs) on various oral cell lines based on the available evidence. This review was registered on PROSPERO (CRD420251183806) and conducted in accordance with PRISMA 2020 guidelines. A systematic search across four major databases (1990-2025) for English-language studies identified in vitro studies assessing GS-AgNPs-induced cytotoxicity in oral cell lines, using assays such as MTT and Annexin V-FITC. The quality of the included studies was evaluated using the QUIN tool for in vitro studies, and the meta-analysis compared cytotoxic responses between normal and cancerous oral cell lines. A total eleven studies met the inclusion criteria, predominantly using the MTT assay to assess cytotoxic responses induced by GS-AgNPs. Two comparative studies (100%) included in the review reported lower toxicity for GS-AgNPs than for conventionally synthesized AgNPs. Cytotoxicity varied with synthesis components, nanoparticle characteristics, concentration, and cell types. GS-AgNPs demonstrated selective cytotoxicity towards oral cancer cell lines, and the meta-analysis confirmed significantly higher cancer-cell sensitivity (p < 0.00001, I² = 7%). Risk-of-bias assessment indicated overall low to moderate bias. In conclusion, green-synthesized silver nanoparticles demonstrated lower cytotoxicity compared with chemically synthesized silver nanoparticles. The GS-AgNPs also exhibited selective cytotoxicity towards oral cancer cell lines, influenced by nanoparticle size, shape, and concentration. Their favorable biocompatibility and selective anticancer activity support their potential application in oral cancer therapy.