Eco-friendly synthesis of betanin-conjugated zinc oxide nanoparticles: antimicrobial efficacy and apoptotic pathway activation in oral cancer cells

Background Phytochemical-based synthesis of nanoparticles (NPs) is an eco-friendly approach with various biomedical applications. Betanin, a natural pigment in beetroot, has antioxidant, anti-inflammatory, and antimicrobial properties. When conjugated with zinc oxide nanoparticles (ZnO NPs), these properties are enhanced. This study aimed to synthesize betanin-ZnO nanoparticles (BE–ZnO–NPs) and evaluate their biological potential. Methods BE–ZnO–NPs were synthesized and characterized using UV-Visible spectroscopy, FTIR, FE-SEM, HR-TEM, EDX, XRD, DLS, and zeta potential analysis. In silico studies assessed interactions with oral pathogen proteins, and antibacterial activity was tested against Enterococcus faecalis , Candida albicans , Staphylococcus aureus and Streptococcus mutans . Antioxidant potential and cytotoxicity on KB cells were evaluated through scavenging assays, MTT assay, and qRT-PCR. Results Betanin synthesized ZnO NPs UV-Vis results showed surface plasmon resonance at 388 nm, and FTIR confirmed betanin role as a capping agent. FE-SEM and TEM revealed particles of 37 nm. EDX confirmed zinc content, and XRD showed a hexagonal structure. Zeta potential was − 3.3 mV, and DLS indicated a size of 38.73 nm. In silico analysis showed strong binding to E. faecalis (− 8.0 Kcal/mol). BE–ZnO–NPs demonstrated antibacterial activity at 100 µg/mL, with inhibition zones of 18 ± 0.14 mm for E. faecalis and 14 ± 0.18 mm for S. mutans . In contrast, BE demonstrated antibacterial activity at 100 µg/mL, with zone of inhibition of 10.6 ± 0.14 mm for E. faecalis and 11.4 ± 0.18 mm for S. mutans. Antioxidant assays revealed dose-dependent scavenging activity. Cytotoxicity showed an IC 50 of 24.29 µg/mL, with qRT-PCR indicating apoptosis through the BCL2/BAX/P53 pathway. Conclusions BE–ZnO–NPs exhibited significant antibacterial and antioxidant activities and demonstrated the ability to induce apoptosis in oral cancer cells via the BCL-2/BAX/P53 signalling pathway. These findings highlight the potential of BE–ZnO–NPs as promising antimicrobial agents for tooth infections and as therapeutic agents for oral tumour treatment.