Peganum harmala leaf extract mediated green synthesised polyvinyl alcohol zinc oxide beta cyclodextrin nanocomposite for anticancer and antimicrobial applications

The present study describes the eco-friendly synthesis and multifunctional investigation of a Peganum harmala leaf extract-mediated PVA/ZnO@β-CD nanocomposite. The synthesised nanocomposite was characterised by UV-Vis, FTIR, and XRD analyses, which confirmed the formation of crystalline ZnO NPs within the PVA/β-CD network. The UV-Vis absorption peak at 354.34 nm indicated quantum confinement effects, while FTIR spectra verified Zn-O bond formation and strong intermolecular interactions among ZnO, β-CD, and PVA. XRD patterns demonstrated the hexagonal wurtzite structure of ZnO with nanoscale crystallinity. Morphological analysis by FE-SEM and HR-TEM revealed uniformly distributed quasi-spherical NPs (15-25 nm) embedded within the polymeric network. Elemental mapping further confirmed the presence of Zn, C, and O as major constituents. Additionally, DLS and zeta potential analyses indicated excellent colloidal stability (-33.62 mV) and a narrow nanosized distribution (299.4 nm). Biological evaluation demonstrated potent, selective anticancer activity of the nanocomposite against MDA-MB-231 triple-negative breast cancer cells, with time-dependent IC₅₀ values of 24.45, 20.83, and 12.74 µg/mL at 24, 48, and 72 h, respectively. In contrast, it exhibited minimal cytotoxicity toward normal HMECs. Mechanistic studies revealed enhanced ROS generation, depletion of antioxidant defences, mitochondrial dysfunction, and induction of apoptosis via the intrinsic pathway, as supported by morphological staining and apoptotic gene modulation. Moreover, the nanocomposite exhibited broad-spectrum antibacterial and antifungal activities, particularly against S. aureus, S. pneumoniae, and Candida species. These results highlight the P. harmala-mediated PVA/ZnO@β-CD nanocomposite as a promising, green-engineered nanotherapeutic candidate with potent anticancer and antimicrobial potential.