Targeted anticancer potential against glioma cells of thymoquinone delivered by mesoporous silica core-shell nanoformulations with pH-dependent release
| Autor: | Iman M Higazy, Ahmed M. Aboul-Enein, Witold Lojkowski, Samar A Shahein, Esam R Ahmed, Khaled AbouAitah, Shaker A. Mousa, Faten Abou-Elella |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
brain cancer targeting
thymoquinone core-shell nanoformulation Pharmaceutical Science Apoptosis Biocompatible Materials 02 engineering and technology Pharmacology 01 natural sciences Chitosan Diffusion chemistry.chemical_compound Drug Delivery Systems International Journal of Nanomedicine Drug Discovery Spectroscopy Fourier Transform Infrared Benzoquinones drug delivery system Cytotoxicity Thymoquinone Original Research biology Calorimetry Differential Scanning Caspase 3 Cytochrome c Brain Cytochromes c General Medicine Glioma Prodrug Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Silicon Dioxide Thermogravimetry 0210 nano-technology Porosity Drug Compounding Biophysics Bioengineering Antineoplastic Agents 010402 general chemistry Biomaterials Inhibitory Concentration 50 Cell Line Tumor medicine Humans mesoporous silica nanoparticles Organic Chemistry Cell Cycle Checkpoints medicine.disease In vitro 0104 chemical sciences Enzyme Activation Drug Liberation Kinetics chemistry pH-dependent release kinetics biology.protein Nanoparticles |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 1176-9114 |
| Popis: | Samar A Shahein1,*Ahmed M Aboul-Enein,1 Iman M Higazy,2 Faten Abou-Elella,1 Witold Lojkowski,3 Esam R Ahmed,4 Shaker A Mousa,5 Khaled AbouAitah3,6,*1Biochemistry Department, Faculty of Agriculture, Cairo University, Giza, Egypt; 2Department of Pharmaceutical Technology, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Giza, Egypt; 3Laboratory of Nanostructures, Institute of High Pressure Physics, Polish Academy of Sciences, Warsaw, Poland; 4Confirmatory Diagnostic Unit, Egyptian Organization for Vaccine, Sera and Biological Products (VACSERA), Giza, Egypt; 5The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, New York, NY, USA; 6Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), Giza, Egypt*These authors contributed equally to this workBackground and purpose: Glioma is one of the most aggressive primary brain tumors and is incurable. Surgical resection, radiation, and chemotherapies have been the standard treatments for brain tumors, however, they damage healthy tissue. Therefore, there is a need for safe anticancer drug delivery systems. This is particularly true for natural prodrugs such as thymoquinone (TQ), which has a high therapeutic potential for cancers but has poor water solubility and insufficient targeting capacity. We have tailored novel core-shell nanoformulations for TQ delivery against glioma cells using mesoporous silica nanoparticles (MSNs) as a carrier.Methods: The core-shell nanoformulations were prepared with a core of MSNs loaded with TQ (MSNTQ), and the shell consisted of whey protein and gum Arabic (MSNTQ-WA), or chitosan and stearic acid (MSNTQ-CS). Nanoformulations were characterized, studied for release kinetics and evaluated for anticancer activity on brain cancer cells (SW1088 and A172) and cortical neuronal cells-2 (HCN2) as normal cells. Furthermore, they were evaluated for caspase-3, cytochrome c, cell cycle arrest, and apoptosis to understand the possible anticancer mechanism.Results: TQ release was pH-dependent and different for core and core-shell nanoformulations. A high TQ release from MSNTQ was detected at neutral pH 7.4, while a high TQ release from MSNTQ-WA and MSNTQ-CS was obtained at acidic pH 5.5 and 6.8, respectively; thus, TQ release in acidic tumor environment was enhanced. The release kinetics fitted with the Korsmeyer–Peppas kinetic model corresponding to diffusion-controlled release. Comparative in vitro tests with cancer and normal cells indicated a high anticancer efficiency for MSNTQ-WA compared to free TQ, and low cytotoxicity in the case of normal cells. The core-shell nanoformulations significantly improved caspase-3 activation, cytochrome c triggers, cell cycle arrest at G2/M, and apoptosis induction compared to TQ.Conclusion: Use of MSNs loaded with TQ permit improved cancer targeting and opens the door to translating TQ into clinical application. Particularly good results were obtained for MSNTQ-WA.Keywords: brain cancer targeting, drug delivery system, thymoquinone core-shell nanoformulation, mesoporous silica nanoparticles, pH-dependent release kinetics |
| Databáze: | OpenAIRE |
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