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Light-Responsive Metal-Organic Frameworks (MOFs) For Doxorubicin Controlled Release

Abdelwahab, Isra
A Master of Science thesis in Biomedical Engineering by Isra Abdelwahab entitled, “Light-Responsive Metal-Organic Frameworks (MOFs) For Doxorubicin Controlled Release”, submitted in April 2023. Thesis advisor is Dr. Rana Sabouni. Soft copy is available (Thesis, Completion Certificate, Approval Signatures, and AUS Archives Consent Form).
The life cycle of human cells involves growth, divisions, and programmed cell death (apoptosis). However, DNA damage can cause some cells to proliferate uncontrollably, leading to cancer. While chemotherapy is an effective treatment option for cancer, it often has significant side effects. Researchers are exploring novel ways to deliver chemotherapy drugs more effectively while minimizing side effects. One promising method for controlled and targeted drug delivery is the use of stimuli light-responsive nanomaterials. Among the various stimuli-responsive nanomaterials, light mechanisms have shown considerable potential in providing site specific drug delivery. Metal-organic frameworks (MOFs) possess unique physicochemical properties, making them a promising candidate as light-responsive nanocarrier for controlled drug delivery. In this work, we investigated the potential of three MOFs, ZIF-8, Fe-BTC, and MIL-53(Al), as light-responsive nanocarriers for the controlled delivery of doxorubicin (DOX). The MOFs were evaluated for their drug encapsulation and release efficiency. The results showed that ZIF-8 exhibited a high encapsulation efficiency of 87%, and a high drug release efficiency at both pH levels of 5.3 and 7.4. On the other hand, Fe-BTC and MIL-53(Al) exhibited dual responsiveness to pH and light, with the highest release occurring at pH 5.3 when exposed to UV light. The total release efficiency of both systems was significantly higher with UV. Additionally, MIL-53(Al) also showed a seven folds higher drug release efficiency with NIR light at pH 5.3 than the control. The physicochemical properties of MOFs were analyzed using SEM, FTIR BET, and XRD. Furthermore, the in vitro cytotoxicity of the MOFs was tested on HCT 116 colon cancer cells using MTT assays, and the results showed that both MIL-53 (Al) and Fe-BTC were biocompatible up to 200 μg/mL, while ZIF-8 had some cytotoxicity. Also, UV-C light alone did not affect cell viability, however, when combined with DOX-Fe-BTC, the cell viability was reduced to 82.25%, while the combination with DOX-MIL-53(Al) had cell viability of 49.84%, indicating that it is a promising treatment option for cancer.
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