5-Fluorouracil-containing inorganic iron oxide/platinum nanozymes with dual drug delivery and enzyme-like activity for the treatment of breast cancer |
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| Affiliation: | 1. Department of Breast Surgery, the First People''s Hospital of Jingzhou, Jingzhou 434000, Hubei Province, China;2. Department of Microbiology, Faculty of Pharmaceutical Science, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran;3. Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong;4. Department of Clinical Sciences, College of Pharmacy and Health Sciences, Ajman University, PO Box 346, Ajman, United Arab Emirates;5. Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates;6. Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Ajman University, PO Box 346, Ajman, United Arab Emirates;7. Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran;8. Department of Nanotechnology, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran;9. Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran;10. Depatment of Tissue Engineering, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran;11. Department of Chemistry, College of Science, Kuwait University, Safat 13060, Kuwait;12. Cardiovascular and Metabolic Sciences Department, Learner Research Institute, Cleveland Clinic, OH 44195, USA |
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| Abstract: | Intrinsic enzyme-mimic activity of inorganic nanoparticles has been widely used for nanozymatic anticancer and antibacterial treatment. However, the relatively low peroxidase-mimic activity (PMA) and catalse-mimic activity (CMA) of nanozymes in tumor microenvironment has hampered their potential application in the cancer therapy. Therefore, in this study, we aimed to fabricate platinum (Pt) nanozymes dispersed on the surface of iron oxide (Fe3O4) nanosphere that, in addition to boosting the PMA and CMA, resulted in the formation of a pH-sensitive nano-platform for drug delivery in breast cancer therapy. After development of Fe3O4 nanospheres containing Pt nanozymes and loading 5-fluorouracil (abbreviated as: Fe3O4/Pt-FLU@PEG nanospheres), the physicochemical properties of the nanospheres were examined by electron microscopy, dynamic light scattering, zeta potential, X-ray diffraction, thermogravimetric, BET surface, and PMA/CMA analyses. Then, the cytotoxicity of the Fe3O4/Pt-FLU@PEG nanospheres against 4T1 cells was investigated by the cell counting kit-8 assay and flow cytometry. Also, the anticancer effect of fabricated nanoplatform was assessed in mouse bearing 4T1 cancer tumors, in vivo. The results showed that the Fe3O4/Pt-FLU@PEG nanospheres provide a platform for optimal FLU loading, continuous pH-sensitive drug release, and potential PMA and CMA to increase the level of ROS and O2, respectively. Cytotoxicity outputs showed that the Fe3O4/Pt-FLU@PEG nanospheres mitigate the proliferation of 4T1 cancer cells mediated by apoptosis and intracellular generation of reactive oxygen species (ROS). Furthermore, in vivo assays indicated a significant reduction in tumor size and overcoming tumor hypoxia. Overall, we believe that the developed nanospheres with dual enzyme-mimic activity and pH-sensitive drug delivery can be used for ROS/chemotherapy double-modality antitumor therapy. |
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| Keywords: | Breast cancer 5-Fluorouracil Nanozymes Cytotoxicity |
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