Incorporation of Zataria multiflora essential oil into chitosan biopolymer nanoparticles: A nanoemulsion based delivery system to improve the in-vitro efficacy, stability and anticancer activity of ZEO against breast cancer cells.

In the search of new alternative anticancer agents, essential oils (Eos) play a critical role, exerting selective anti-cancer properties and limiting the toxicity of conventional therapies. However, these compounds still face some challenges. Nanoemulsification (NE) protects labile and sensitive EO ingredients until they are released in the system. Herein, Zataria Multiflora Essential Oil (ZEO) loaded into chitosan (CS) nanoparticles was prepared in aqueous solution by mild emulsification into nanometric particles. FTIR spectroscopy exhibited no covalent interaction between active groups of ZEO and functional groups of CS. The outcomes revealed that CS/ZEONE increasingly improves the proliferation inhibition rate of Breast cancer cells as confirmed by MTT, morphological changes, DNA fragmentation and FACS analyses. Our findings suggested that CS/ZEONE exposure induces apoptosis, generates ROS, and triggers mitochondrial membrane permeabilization as well as DNA damage without harming normal cells. To find out the mechanism more precisely, the interaction of CS/ZEONE with gDNA was elucidated and Intercalative binding with strong stabilization of the DNA helix has been proposed. In conclusion, our data suggested that CS/ZEONE can be further explored as a promising antiproliferative and therapeutic candidate against breast cancer.