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

Abstract

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 in vitro 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.