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Preparation and Characterization of Smart Carbon-based Nanocarriers Modified with Polymers for Targeting Delivery of Anticancer Drugs

Asgari, Shadi | 2020

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 53113 (03)
  4. University: Sharif University of Technology
  5. Department: Chemistry
  6. Advisor(s): Pourjavadi, Ali
  7. Abstract:
  8. The use of nanocarriers has been recently considered for targeted drug delivery. In the targeted drug delivery systems, drug is directed to the target tissue and its adverse effects are reduced on the healthy tissues. Graphene oxide and hollow mesoporous carbon nanospheres are two types of the most interesting carbon-based nanocarriers because of their unique properties. Aim of the thesis has been the synthesis of the nanocarriers based-on graphene oxide and hollow mesoporous carbon nanospheres and their surface modifications by magnetic polyamidoamine dendrimer and oxygen-rich polymers such as poly(epichlorohydrin) and hyperbranched polyglycerol. These modifications result in higher hydrophilicity, biocompatibility, biodegradability, and cellular uptake for the targeted drug delivery. Characterization of the prepared nanocarriers was performed by Fourier transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TGA), ultraviolet-visible (UV-Vis) and other analyses. These nanocarriers displayed sensitivity to the internal and external stimuli such as pH and external magnetic field and were used for targeted and controlled release of anticancer drugs including Doxorubicin (DOX), Curcumin (Cur), and Paclitaxel (PTX). Loading of the drugs was performed and their release behaviors were investigated at 37oC in pH 7.4 and pH 5.0. The release profiles indicated a pH-sensitive behavior as well as a sustained and controlled release behavior of the drugs. Co-delivery and synergistic effect of DOX and Cur as well as PTX and Cur drugs were investigated in the systematic breast cancer and local breast cancer chemotherapy. The results of cytotoxicity (MTT) and cellular uptake studies (both confocal microscopy and flow cytometry) confirmed the synergistic effect of the couple drugs. Cur enhanced cytotoxicity and cellular uptake of the PTX/Cur-loaded nanocarrier and DOX/Cur-loaded nanocarrier compared to PTX-loaded nanocarrier and DOX-loaded nanocarrier . Also, PTX and Cur combination not only used to treat breast cancer but also prevents the recurrence of the cancer tumor. While using the prepared nanocarriers in the chemotherapy, the magnetic nanocarrier would also be used in hyperthermia therapy because of the iron oxide magnetic nanoparticles. In addition, the synergistic effect of DOX and calcium ions was investigated to treat HeLa cancer cells. The synergistic effect was confirmed by MTT as well as cellular uptake experiments
  9. Keywords:
  10. Targeted Druy Delivery ; Graphene Oxide ; Synergistic Effect ; Anticancer Drugs ; Oxigen Rich Polymers ; Hollow Mesoporous Carbon ; Magnetic Dendrimer ; Stimuli-Sensitive

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