Zeolite Nanoparticles Loaded with 2-Methoxystradiol As a Novel Drug Delivery System for the Prostate Cancer Therapy

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Jul 14

PMID 37446151

Authors

Denisse Mena-Silva

Aline Alfaro

Andrea Leon

Emanuel Guajardo-Correa

Estefania Elgueta

Patricia Diaz

Cristian Vilos

Hugo Cardenas

Juliano C Denardin

Pedro A Orihuela

Affiliations

Soon will be listed here.

Abstract

The estrogen metabolite 2-methoxyestradiol (2ME) is a promissory anticancer drug mainly because of its pro-apoptotic properties in cancer cells. However, the therapeutic use of 2ME has been hampered due to its low solubility and bioavailability. Thus, it is necessary to find new ways of administration for 2ME. Zeolites are inorganic aluminosilicates with a porous structure and are considered good adsorbents and sieves in the pharmaceutical field. Here, mordenite-type zeolite nanoparticles were loaded with 2ME to assess its efficiency as a delivery system for prostate cancer treatment. The 2ME-loaded zeolite nanoparticles showed an irregular morphology with a mean hydrodynamic diameter of 250.9 ± 11.4 nm, polydispersity index of 0.36 ± 0.04, and a net negative surface charge of -34 ± 1.73 meV. Spectroscopy with UV-vis and Attenuated Total Reflectance Infrared Fourier-Transform was used to elucidate the interaction between the 2ME molecules and the zeolite framework showing the formation of a 2ME-zeolite conjugate in the nanocomposite. The studies of adsorption and liberation determined that zeolite nanoparticles incorporated 40% of 2ME while the liberation of 2ME reached 90% at pH 7.4 after 7 days. The 2ME-loaded zeolite nanoparticles also decreased the viability and increased the mRNA of the 2ME-target gene F-spondin, encoded by SPON1, in the human prostate cancer cell line LNCaP. Finally, the 2ME-loaded nanoparticles also decreased the viability of primary cultures from mouse prostate cancer. These results show the development of 2ME-loaded zeolite nanoparticles with physicochemical and biological properties compatible with anticancer activity on the human prostate and highlight that zeolite nanoparticles can be a good carrier system for 2ME.

References

Serati-Nouri H, Jafari A, Roshangar L, Dadashpour M, Pilehvar-Soltanahmadi Y, Zarghami N . Biomedical applications of zeolite-based materials: A review. Mater Sci Eng C Mater Biol Appl. 2020; 116:111225. DOI: 10.1016/j.msec.2020.111225. View

Vilos C, Morales F, Solar P, Herrera N, Gonzalez-Nilo F, Aguayo D . Paclitaxel-PHBV nanoparticles and their toxicity to endometrial and primary ovarian cancer cells. Biomaterials. 2013; 34(16):4098-4108. DOI: 10.1016/j.biomaterials.2013.02.034. View

Wang Y, Guo R, Cao X, Shen M, Shi X . Encapsulation of 2-methoxyestradiol within multifunctional poly(amidoamine) dendrimers for targeted cancer therapy. Biomaterials. 2011; 32(12):3322-9. DOI: 10.1016/j.biomaterials.2010.12.060. View

Danyuo Y, Ani C, Salifu A, Obayemi J, Dozie-Nwachukwu S, Obanawu V . Anomalous Release Kinetics of Prodigiosin from Poly-N-Isopropyl-Acrylamid based Hydrogels for The Treatment of Triple Negative Breast Cancer. Sci Rep. 2019; 9(1):3862. PMC: 6405774. DOI: 10.1038/s41598-019-39578-4. View

Sawaftah N, Paul V, Awad N, Husseini G . Modeling of Anti-Cancer Drug Release Kinetics From Liposomes and Micelles: A Review. IEEE Trans Nanobioscience. 2021; 20(4):565-576. DOI: 10.1109/TNB.2021.3097909. View

Lowes L, Lock M, Rodrigues G, DSouza D, Bauman G, Ahmad B . The significance of circulating tumor cells in prostate cancer patients undergoing adjuvant or salvage radiation therapy. Prostate Cancer Prostatic Dis. 2015; 18(4):358-64. PMC: 4788488. DOI: 10.1038/pcan.2015.36. View

Parada-Bustamante A, Valencia C, Reuquen P, Diaz P, Rincion-Rodriguez R, Orihuela P . Role of 2-methoxyestradiol, an Endogenous Estrogen Metabolite, in Health and Disease. Mini Rev Med Chem. 2015; 15(5):427-38. DOI: 10.2174/1389557515666150226121052. View

Bosland M, Schlicht M, Acevedo N, Soto A, Prins G . Effects of perinatal exposure to bisphenol A on induction of prostate cancer in Sprague Dawley rats by MNU and testosterone. Toxicology. 2022; 484:153394. PMC: 9945469. DOI: 10.1016/j.tox.2022.153394. View

Nel A, Madler L, Velegol D, Xia T, Hoek E, Somasundaran P . Understanding biophysicochemical interactions at the nano-bio interface. Nat Mater. 2009; 8(7):543-57. DOI: 10.1038/nmat2442. View

10.

de Gennaro B, Catalanotti L, Cappelletti P, Langella A, Mercurio M, Serri C . Surface modified natural zeolite as a carrier for sustained diclofenac release: A preliminary feasibility study. Colloids Surf B Biointerfaces. 2015; 130:101-9. DOI: 10.1016/j.colsurfb.2015.03.052. View

11.

Orostica M, Reuquen P, Guajardo-Correa E, Parada-Bustamante A, Cardenas H, Orihuela P . Sperm utilize tumor necrosis factor alpha to shut down a 2-methoxyestradiol nongenomic pathway that accelerates oviductal egg transport in the rat. Reproduction. 2023; 165(4):383-393. DOI: 10.1530/REP-22-0289. View

12.

Alhakamy N, Al-Rabia M, Asfour H, Alshehri S, Alharbi W, Halawani A . 2-Methoxy-estradiol Loaded Alpha Lipoic Acid Nanoparticles Augment Cytotoxicity in MCF-7 Breast Cancer Cells. Dose Response. 2022; 19(4):15593258211055023. PMC: 8669132. DOI: 10.1177/15593258211055023. View

13.

Cacciatore A, Albino D, Catapano C, Carbone G . Preclinical Models of Neuroendocrine Prostate Cancer. Curr Protoc. 2023; 3(5):e742. DOI: 10.1002/cpz1.742. View

14.

Derakhshankhah H, Jafari S, Sarvari S, Barzegari E, Moakedi F, Ghorbani M . Biomedical Applications of Zeolitic Nanoparticles, with an Emphasis on Medical Interventions. Int J Nanomedicine. 2020; 15:363-386. PMC: 6983480. DOI: 10.2147/IJN.S234573. View

15.

Chutia P, Kato S, Kojima T, Satokawa S . Adsorption of As(V) on surfactant-modified natural zeolites. J Hazard Mater. 2008; 162(1):204-11. DOI: 10.1016/j.jhazmat.2008.05.024. View

16.

Hao J, Stavljenic Milasin I, Batu Eken Z, Mravak-Stipetic M, Pavelic K, Ozer F . Effects of Zeolite as a Drug Delivery System on Cancer Therapy: A Systematic Review. Molecules. 2021; 26(20). PMC: 8540241. DOI: 10.3390/molecules26206196. View

17.

Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A . Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics. 2018; 10(2). PMC: 6027495. DOI: 10.3390/pharmaceutics10020057. View

18.

Chang A, Autio K, Roach 3rd M, Scher H . High-risk prostate cancer-classification and therapy. Nat Rev Clin Oncol. 2014; 11(6):308-23. PMC: 4508854. DOI: 10.1038/nrclinonc.2014.68. View

19.

Ravichandiran P, Jegan A, Premnath D, Periasamy V, Muthusubramanian S, Vasanthkumar S . Synthesis, molecular docking and cytotoxicity evaluation of novel 2-(4-amino-benzosulfonyl)-5H-benzo[b]carbazole-6,11-dione derivatives as histone deacetylase (HDAC8) inhibitors. Bioorg Chem. 2014; 53:24-36. DOI: 10.1016/j.bioorg.2014.01.002. View

20.

Calvo B, Canoira L, Morante F, Martinez-Bedia J, Vinagre C, Garcia-Gonzalez J . Continuous elimination of Pb2+, Cu2+, Zn2+, H+ and NH4 + from acidic waters by ionic exchange on natural zeolites. J Hazard Mater. 2009; 166(2-3):619-27. DOI: 10.1016/j.jhazmat.2008.11.087. View