Bi-functional nature of nanoceria: pro-drug and drug-carrier potentiality towards receptor-mediated targeting of doxorubicin
| Autor: | Alok P. Jakhade, Madhura A. Damle, Rajeev C. Chikate, Ruchika Kaul-Ghanekar, Varsha Shetty |
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| Rok vydání: | 2020 |
| Předmět: |
DNA damage
Chemistry 02 engineering and technology General Chemistry Prodrug 010402 general chemistry 021001 nanoscience & nanotechnology 01 natural sciences Redox Catalysis 0104 chemical sciences Materials Chemistry medicine Biophysics Doxorubicin Nanocarriers 0210 nano-technology Drug carrier Cytotoxicity Nanoconjugates medicine.drug |
| Zdroj: | New Journal of Chemistry. 44:17013-17026 |
| ISSN: | 1369-9261 1144-0546 |
| DOI: | 10.1039/d0nj02895a |
| Popis: | Nanoceria is considered to be a promising material for the modulation of its pro-and anti-oxidant activities due to its tuneable Ce3+/Ce4+ ratios under different physiological conditions. In the present study, we explored the feasibility of CeO2 NPs as a pro-drug and drug carrying vehicle towards receptor-mediated targeted delivery of doxorubicin (DOX) to MCF-7 cancer cells. The surface-engineered, substancilly smaller sized (3–4 nm) particles of CeO2-loaded DOX-nanoconjugates possess excellent dispersibility in water, with surface charges in the range of +17.03 to −7.68 mV. The functionalised nanoceria exhibits a quasi-reversible Ce3+/Ce4+ redox couple at a considerably lower redox potential, while the amount of DOX loaded on the nanoceria was found to be in the range of 2.3–12%. The DNA binding and cleavage activities of CeO2 NPs suggest their beneficial binding with phosphate linkages that induces DNA damage. Uncoated and PEGylated CeO2 NPs possess significant anticancer activity against MCF-7, with the latter exhibiting better activity at 2.5 μg mL−1 due to its interference in cellular redox reactions induced by reactive oxygen species (ROS). Moreover, the synergic conjugation of nanoceria with DOX resulted in excellent cytotoxicity of these nanoconjugates against MCF-7 cells at an extremely low concentration (57.5 ng mL−1) of DOX. This feature can be ascribed to the enhanced uptake of nanoceria as well as site targeting of DOX nanoconjugates facilitated by the folic acid (FA) via folate receptors. Thus, it may be concluded that nanoceria behaves in a dual manner both as a pro-drug and an efficient nanocarrier for delivery of DOX at a specific site. |
| Databáze: | OpenAIRE |
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