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.
Similar content being viewed by others
References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Erci F, Cakir-Koc R, Isildak I. Green synthesis of silver nanoparticles using Thymbra spicata L. var. spicata (Zahter) aqueous leaf extract and evaluation of their morphology dependent antibacterial and cytotoxic activity. Artif Cells Nanomed Biotechnol. 2018;46(sup1):150–8.
Palanisamy S, Wang YM. Superparamagnetic iron oxide nanoparticulate system: synthesis, targeting, drug delivery and therapy in cancer. Dalton Trans. 2019;48(26):9490–515.
Sanna V, Pala N, Sechi M. Targeted therapy using nanotechnology: focus on cancer. Int J Nanomedicine. 2014;9:467–83.
Yalcin S. Dextran-coated iron oxide nanoparticle for delivery of miR-29a to breast cancer cell line. Pharm Dev Technol. 2019;24(8):1032–7.
Arias LS, Pessan JP, Vieira APM, Lima TMT, Delbem ACB, Monteiro DR. Iron oxide nanoparticles for biomedical applications: a perspective on synthesis, drugs, antimicrobial activity, and toxicity. Antibiotics (Basel). 2018 ;7(2). pii: E46.
Yalcin S, Khodadust R, Unsoy G, Ceren Garip I, Didem Mumcuoglu Z, Gunduz U. Synthesis and characterization of polyhydroxybutyrate coated magnetic nanoparticles: toxicity analyses on different cell lines. Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistry. 2015;45(5):700–8.
Vandamme P, Coenye T. Taxonomy of the genus Cupriavidus: a tale of lost and found. Int J Syst Evol Microbiol. 2004;54(Pt 6):2285–9.
Bonartsev AP, Myshkina VL, Nikolaeva DA, Furina EK, Makhina TA, Livshits VA, et al. Biosynthesis, biodegradation, and application of poly (3-hydroxybutyrate) and its copolymers-natural polyesters produced by diazotrophic bacteria. Communicating Current Research and Educational Topics and Trends in Applied Microbiology. 2007;1:295–307.
Jendrossek D, Handrick R. Microbial degradation of polyhydroxyalkanoates. Annu Rev Microbiol. 2002;56:403–32.
Jacobo-Herrera N, Pérez-Plasencia C, Castro-Torres VA, Martínez-Vázquez M, González-Esquinca AR, Zentella-Dehesa A. Selective acetogenins and their potential as anticancer agents. Frontiers in Pharmacology. 2019:10.
Coria-Téllez AV, Montalvo-Gónzalez E, Yahia EM, Obledo-Vázquez EN. Annona muricata: a comprehensive review on its traditional medicinal uses, phytochemicals, pharmacological activities, mechanisms of action and toxicity. Arab J Chem. 2018;11(5):662–91.
Gavamukulya Y, Wamunyokoli F, El-Shemy HA. Annona muricata: is the natural therapy to most disease conditions including cancer growing in our backyard? A systematic review of its research history and future prospects. Asian Pac J Trop Med. 2017;10(9):835–48.
Gavamukulya Y, El-Shemy HA, Meroka AM, Madivoli ES, Maina EN, Wamunyokoli F, et al. Advances in green nanobiotechnology: data for synthesis and characterization of silver nanoparticles from ethanolic extracts of fruits and leaves of Annona muricata. Data Brief. 2019;25:104194.
Sabapati M, Palei NN, AK CK, Molakpogu RB. Solid lipid nanoparticles of Annona muricata fruit extract: formulation, optimization and in vitro cytotoxicity studies. Drug Dev Ind Pharm. 2019;45(4):577–86.
Rupprecht JK, Hui YH, McLaughlin JL. Annonaceous acetogenins: a review. J Nat Prod. 1990;53(2):237–78.
McLaughlin JL. Paw paw and cancer: annonaceous acetogenins from discovery to commercial products. J Nat Prod. 2008;71:1311–21.
Degli Esposti M, Ghelli A, Ratta M, Cortes D, Estornell E. Natural substances (acetogenins) from the family Annonaceae are powerful inhibitors of mitochondrial NADH dehydrogenase (complex I). Biochem J. 1994;301(Pt 1):161–7.
Ribeiro AF, Santos JF, Mattos RR, Barros EGO, Nasciutti LE, Cabral LM, et al. Characterization and in vitro antitumor activity of polymeric nanoparticles loaded with Uncaria tomentosa extract. An Acad Bras Cienc. 2020;92(1):e20190336.
Piazzini V, Vasarri M, Degl'Innocenti D, Guastini A, Barletta E, Salvatici MC, et al. Comparison of chitosan nanoparticles and soluplus micelles to optimize the bioactivity of Posidonia oceanica extract on human neuroblastoma cell migration. Pharmaceutics. 2019;11(12):pii: E655.
Moghadamtousi SZ, Fadaeinasab M, Nikzad S, Mohan G, Ali HM, Kadir HA. Annona muricata (Annonaceae): a review of its traditional uses, isolated acetogenins and biological activities. Int J Mol Sci. 2015;16(7):15625–58.
Xiong YC, Yao YC, Zhan XY, Chen GQ. Application of polyhydroxyalkanoates nanoparticles as intracellular sustained drug-release vectors. J Biomater Sci Polym Ed. 2010;21(1):127–40.
Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, … . Nakatsuji H. Gaussian09 Revision D. 01, Gaussian Inc. Wallingford CT. 2009. See also: URL: http://www.gaussian.com.
Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, et al. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem. 1998;19(14):1639–62.
Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010 Jan 30;31(2):455–61.
Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics. J Mol Graph. 1996;14(1):33–8 27-8.
Thomsen R, Christensen MH. MolDock: a new technique for high-accuracy molecular docking. J Med Chem. 2006;49(11):3315–21.
Badrie N, Schauss AG. Soursop (Annona muricata L.): composition, nutritional value, medicinal uses, and toxicology in bioactive foods in promoting health. Academic Press. 2010:621–43.
Robles JF, Muñoz K, Rivera N, Suarez E. Anti-proliferative properties of methanolic extracts of Annona muricata in colon, lung and skin cancer cell lines. FASEB J. 2017;31:807–5.
Kim GS, Zeng L, Alali F, Rogers LL, Wu FE, McLaughlin JL, et al. Two new mono-tetrahydrofuran ring acetogenins, annomuricin E and muricapentocin, from the leaves of Annona muricata. J Nat Prod. 1998;61(4):432–6.
Eggadi V, Gundamedi S, Sheshagiri SBB, Revoori SK, Jupally VR, Kulandaivelu U. Evaluation of anticancer activity of Annona muricata in 1, 2-dimethyl hydrazine induced colon cancer. World Appl Sci J. 2014;32:444–50.
Deep G, Kumar R, Jain AK, Dhar D, Panigrahi GK, Hussain A, et al. Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity. Sci Rep. 2016;6:23135.
Rady I, Bloch MB, Chamcheu RN, Banang Mbeumi S, Anwar MR, Mohamed H, et al. Anticancer properties of graviola (Annona muricata): a comprehensive mechanistic review. Oxidative Med Cell Longev. 2018;2018:1826170.
Antony P, Vijayan R. Acetogenins from Annona muricata as potential inhibitors of antiapoptotic proteins: a molecular modeling study. Drug Des Devel Ther. 2016;10:1399–410.
Lannuzel A, Höglinger GU, Champy P, Michel PP, Hirsch EC, Ruberg M. Is atypical parkinsonism in the Caribbean caused by the consumption of Annonacae? J Neural Transm Suppl. 2006;70:153–7.
Acknowledgments
This research was supported by Kirsehir Ahi Evran University Scientific Research Projects FEF.A4.17.018 (2018–2019).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
None declared.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article is part of the Topical Collection on Nanodrugs
Rights and permissions
About this article
Cite this article
Köksal, R., Yalcin, S. The Cytotoxic Effect of Annona muricata-Loaded PHB-Coated Magnetic Nanoparticles on Cancer Cell Lines and Molecular Docking Analyses. Curr Pharmacol Rep 6, 121–130 (2020). https://doi.org/10.1007/s40495-020-00220-x
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40495-020-00220-x