Nerolidol loaded beta cyclodextrin nanoparticles: a promising strategy for inducing apoptosis in breast cancer cells (MCF-7)

This study investigates the synthesis, characterization and anticancer efficacy of nerolidol-loaded beta cyclodextrin polymeric nanoparticles (NER-βCD-NPs) against MCF-7 breast cancer cells. Nerolidol, a sesquiterpene with anti-inflammatory, antioxidant, antimicrobial and anticancer properties, faces challenges of poor solubility and bioavailability, limiting its therapeutic potential. Breast cancer, a leading cause of cancer-related deaths in women, necessitates alternative therapies with fewer side effects compared to conventional chemotherapy. NER-βCD-NPs were synthesized and characterized using UV-visible spectroscopy, fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), dynamic light scattering (DLS), zeta potential analysis and differential scanning calorimetry (DSC). Drug encapsulation efficiency and <i>in vitro</i> release were analyzed using HPLC, while molecular docking assessed NER-βCD interactions. Characterization confirmed successful nanoparticle synthesis. UV-visible spectra and FTIR indicated encapsulation-specific changes, SEM revealed surface morphology, and DLS, zeta potential and DSC analyses demonstrated increased size and stability. The encapsulation efficiency was 84.9%, with 86% NER release at pH 5.4 over 48 h. Docking studies supported strong binding between NER and βCD (binding energy: -3.55 kcal/mol). Cytotoxicity assays showed significant MCF-7 cell inhibition. Mechanistic studies revealed reactive oxygen species (ROS) generation, mitochondrial dysfunction, nuclear changes and cell cycle arrest in the G0-G1 phase. Molecular analysis demonstrated apoptosis through upregulation of Bax, Caspase 6, Caspase 9 and Cytochrome c, alongside Bcl-2 downregulation. These results highlight NER-βCD-NPs as a promising strategy for breast cancer therapy, offering targeted delivery and enhanced therapeutic efficacy while mitigating nerolidol limitations. Further studies are warranted to validate their potential in clinical applications.