The Cytotoxic Effect of Annona muricata -Loaded PHB-Coated Magnetic Nanoparticles on Cancer Cell Lines and Molecular Doc

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NANODRUGS (ATY LAU, SECTION EDITOR)

The Cytotoxic Effect of Annona muricata-Loaded PHB-Coated Magnetic Nanoparticles on Cancer Cell Lines and Molecular Docking Analyses Rana Köksal 1 & Serap Yalcin 2 Published online: 13 June 2020 # Springer Nature Switzerland AG 2020

Abstract In this study, we designed PHB-coated iron oxide–based nanoparticle for the delivery of Annona muricata to breast cancer cells and analyzed its therapeutic efficacy in vitro. The structural properties, functional groups, size distribution, and magnetic properties of the synthesized PHB-coated magnetic nanoparticles (MNPs) were characterized in our previous study. The current study visualized protein–ligand interactions by the use of molecular docking. The plant extract was loaded onto PHB-MNPs in different concentrations and the release efficiencies at different pHs were studied under in vitro conditions. The most efficient loading concentration was found about 55% in pH 7.4. The extract-loaded MNPs were stable up to 3 months in neutral pH for mimicking physiological conditions. The release studies were performed with acetate buffer (pH 4.2) that mimics endosomal pH. The plant extract-loaded PHB-MNPs were about 2.5–3-fold more cytotoxic as compared with free plant extract on HeLa and MDA-MB-231 in vitro, respectively. The cytotoxicity results also confirm that anti-apoptotic proteins have the best docking score for isoquercetin–PHB-MNPs, roseoside–PHB-MNPs, and anonaine–PHB-MNPs with molecular docking analyses. Based on the results obtained, this system can be used effectively in cancer treatment. Keywords Annona muricata . PHB-MNPs . Extract-loaded PHB-MNPs . In vitro cytotoxicity . Cancer cells . Molecular docking

Introduction In the last century, nanotechnology has attracted attention due to its many unique physical and chemical features, and wide applications especially in medicine and biotechnology research [1]. Iron oxide nanoparticles have been used as the most potential nanoparticle systems for cancer treatment, owing to their super-paramagnetic and surface modification properties [2]. Studies have suggested that iron oxide nanoparticles can be an excellent route for targeted drug delivery in cancer treatment [3, 4].

This article is part of the Topical Collection on Nanodrugs * Serap Yalcin [email protected]; [email protected] 1

Department of Advanced Technology, Kırsehir Ahi Evran University, Kırsehir, Turkey

2

Department of Molecular Biology and Genetics, Kırsehir Ahi Evran University, Kırsehir, Turkey

Different organic and inorganic coatings play an important role in the nano-based drug carrier systems capacity [5]. Polymeric magnetic nanoparticles have been used in targeted drug delivery extensively for various active compounds including drug, siRNA, miRNA, extract, and so on. Polyhydroxybutyrate (PHB) are biodegradable polymers used in nanoparticles due to their biocompatibility and continuous-release properties [6–9]. Therefore, new drug discovery aims to extinguish the toxicity of chemotherapeutic agents, de