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Ultrasonically Triggered Release of Folic Acid-Conjugated Liposomes for Breast Cancer Therapy Within Microfluidic Devices
AlHazaimeh, Taima Khair Alla
AlHazaimeh, Taima Khair Alla
Date
2024-05
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35.232-2024.76a Taima Khair Alla AlHazaimeh.pdf
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Description
A Master of Science thesis in Chemical Engineering by Taima Khair Alla AlHazaimeh entitled, “Ultrasonically Triggered Release of Folic Acid-Conjugated Liposomes for Breast Cancer Therapy Within Microfluidic Devices”, submitted in May 2024. Thesis advisor is Dr. Ghaleb Husseini and thesis co-advisor is Dr. Mohamed Abdelgawad. Soft copy is available (Thesis, Completion Certificate, Approval Signatures, and AUS Archives Consent Form).
Abstract
Cancer, among the deadliest diseases, is characterized by the uncontrolled growth and spread of abnormal cells in the body. Chemotherapy, a widely employed treatment for cancer, specifically targets and eliminates rapidly dividing cells, a key characteristic of cancerous cells. However, this approach also affects numerous healthy cells throughout the body that naturally grow fast, leading to severe side effects due to the lack of precision in chemotherapy. Smart Drug Delivery Systems (SDDSs) comprise the encapsulation of therapeutic drugs inside nanoparticles that can deliver the drug exclusively to the tumor site, resulting in fewer side effects. SDDSs leverage the leaky nature of cancer tumor vasculature, allowing nanoparticles to permeate and accumulate more efficiently at the tumor site. Additionally, SDDSs include functionalizing the surface of the nanocarriers to enhance stealth properties, thereby prolonging the lifespan of nanocarriers within the body. Ligands that are also attached to the nanoparticle surface bind to their corresponding receptors, which are overexpressed on cancer cells, facilitating internalization via the endocytic pathway. Moreover, triggering mechanisms, such as ultrasound in this work, could be incorporated to enhance the release of the encapsulated drug exclusively at the tumor site. However, the translation of smart drug delivery systems to clinical trials is limited by the lack of drug screening systems that can mimic the in vivo environment. To overcome this drawback, microfluidic devices provide a powerful tool that can be introduced for drug screening. In this work, we encapsulate the well-known chemotherapy drug Doxorubicin inside PEGylated liposomes, with folic acid attached to the surface of the liposomes to achieve active targeting. In addition, Low-Frequency Ultrasound (LFUS) is used as a triggering mechanism to induce sonoporation and enhance drug release. The drug's performance is tested on a folic acid receptor-positive cell line (MDA-MB-231) and a folic acid receptor-negative cell line (NIH-3T3) achieved by cell culturing inside microchannels. The in vitro experimental results of this research indicate a significantly increased cellular uptake of the anti-cancer drug encapsulated in targeted liposomes with the receptor-positive cell line and an improved cellular uptake upon exposure to LFUS.