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Green Synthesis, Characterization and Application of the Nanomaterials Based on Aluminum Fumarate Metal-Organic Frameworks for Targeted and Smart Delivery and Release of Doxorubicin

Abbariki, Nikzad | 2022

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 55455 (03)
  4. University: Sharif University of Technology
  5. Department: Chemistry
  6. Advisor(s): Bagherzadeh, Mojtaba
  7. Abstract:
  8. In this research, an attempt was made to increase the efficiency and effectiveness of the targeted and controlled release systems of the anticancer drug (doxorubicin) by using inorganic and organic compounds as well as inorganic-organic hybrids. For this purpose, a whole class of aluminum fumarate metal-organic frameworks-based and reduced-graphene oxide nanocarriers were synthesized and using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction spectroscopy (XRD), scanning electron microscope (FESEM) and atomic force microscope (AFM) analysis were characterized, and their nano-composites based on organotin-complexes with the approach of achieving a stable drug delivery system, high drug loading efficiency, very low cytotoxicity and also sensitive to acidic environments designed and synthesized. Drug loading efficiency for synthesized nanocarriers A-520(W)@rGO@Sn(bpy)@DOX, A-520(W)@rGO@Sn(bpy)@DOX@TPE, A-520(TPE)@rGO@Sn(bpy)@DOX and A-520(TPE)@rGO@Sn(bpy)@DOX@TPE are 40/6, 56/1, 48/7 and 59.1% respectively. Drug release from synthesized nanomaterials was investigated at pH 5.5 and 7.2 for more than 600 hours. In nanocarriers without extract coating, drug release was not significantly sequential and was about 28% more than coated nanocarriers. Also, in both nanocarriers based on A-520(W) and A-520(TPE), rapid release occurred without any drug release control in the first 10 hours. The results of MTT on MCF-7 and HEK-293 cell lines showed that tangerine peel extract, which partially covered the surface and porosity of A-520, reduced the cytotoxicity caused by ligands and metals in the metal-organic framework. The cell viability for A-520(W) and A-520(TPE) in MCF-7 cell line is 65% and 90%, respectively, and in HEK-293 cell line, 63% and 73%, respectively. The free synthesized organotin complex showed relatively high cytotoxicity in both cell lines; So that after 72 hours of treatment, more than 55% of the cells died in both cell lines. The toxicity of nanocarriers is controlled by tangerine peel extract, so that cell viability for A-520(TPE)@rGO@Sn(bpy)@TPE nanocarrier after 24 hours of treatment in MCF-7 cell lines and HEK-293 are about 90% and 95%, respectively, and with the addition of the doxorubicin, the toxicity increases dramatically, so, for the A-520(TPE)@rGO@Sn(bpy)@DOX@TPE nanocarrier, at similar conditions, cell viability is 55% and 70%, respectively. The targeted delivery of the drug to the nucleus and cytoplasm of the MCF-7 cell line was investigated by fluorescence microscopy, and the results confirmed the successful and targeted delivery of doxorubicin to the cytoplasm of the target cells.
  9. Keywords:
  10. Doxorubicin ; Green Chemistry ; Drug Delivery ; Metal-Organic Framework ; Controlled Release ; Reduced Graphene Oxide ; Organotin Compounds ; Aluminum Fumarate

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