A Master of Science thesis in Chemical Engineering by Ahmed H.S Ahmed entitled, “Functionalized Metal Organic Frameworks For Chemotherapy Drug Delivery”, submitted in November 2020. Thesis advisor is Dr. Rana Sabouni and thesis co-advisor is Dr. Ghaleb Husseini. Soft copy is available (Thesis, Completion Certificate, Approval Signatures, and AUS Archives Consent Form).
Cancer is the leading cause of death worldwide, and can be treated by various methods or sometimes a combination of different treatments. Chemotherapy is one of the conventional methods of treatment. Although it is effective in killing cancer cells, it affects other fast-growing healthy cells, resulting in several significant health issues. Metal organic frameworks (MOFs) gained tremendous scientific attention for their extraordinary physical and chemical properties. The use of metal organic frameworks was investigated in many applications, and recently they have been used in biomedical applications such as drug delivery. This work aims to investigate an engineered PEG-folate-functionalized metal organic framework as anticancer nanocarriers, specifically targeting cancerous via the folate moiety and using ultrasound as an external stimulus. An iron-based MOF was synthesized under microwave irradiation using FeCl₃.6 (H₂O) and 2-Aminoterephthalic acid (NH₂-BDC) Furthermore, the synthesized MOF was surface modified to conjugate a folic acid group that allows for the active targeting of cancer cells. The synthesized MOF was characterized using Fourier-Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA) and Dynamic Light Scattering (DLS). The encapsulation efficiencies and release profiles of the prepared MOF samples were studied using a model drug (namely calcein) and an anticancer drug (namely Doxorubicin, DOX) under different pH values (5, 6.4, and 7.4) with and without ultrasound. The encapsulation efficiency was determined to be in the range of 88-90% for calcein and 95-97% for DOX under pHs of 5, 6.4, and 7.4, respectively. Furthermore, low-frequency ultrasound (at 35 kHz) demonstrated the sono-sensitivity of PEG-folate-functionalized MOFs samples with release efficiencies of 44.4 % for DOX at 7.4 pH, 70.2% at 5.3 pH with PEG-FA modification, and 90% at 5.3 pH without PEG-FA modification within 280 mins compared to a control study (without ultrasound) of 14%, 14%, and 16%, respectively. Moreover, the release kinetics of both studies were studied and fitted to 9 different drug release models. Finally, statistical analysis confirms the significance of ultrasound triggered release. Accordingly, it is anticipated that using ultrasound as an external triggering mechanism with MOFs will help initiate a new generation of smart drug delivery systems in the fight against cancer.