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Ultrasound-triggered Release of Calcein from Glucose Transporter 1 (GLUT1) Inhibitor-Targeted Liposomes
Hatami, Sedigheh
Hatami, Sedigheh
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35.232-2025.79a Sedigheh Hatami_COMPRESSED.pdf
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Description
A Master of Science thesis in Biomedical Engineering by Sedigheh Hatami entitled, “Ultrasound-triggered Release of Calcein from Glucose Transporter 1 (GLUT1) Inhibitor-Targeted Liposomes”, submitted in November 2025. Thesis advisor is Dr. Ghaleb A. Husseini. Soft copy is available (Thesis, Completion Certificate, Approval Signatures, and AUS Archives Consent Form).
Abstract
This thesis explores a targeted drug delivery strategy using low-frequency ultrasound (LFUS) to trigger the release of therapeutic agents from nanocarriers. This work is important because Glucose Transporter 1 (GLUT1) is overexpressed on many cancers, and WZB117 is one of the few ligands capable of blocking this transporter across diverse tumors. Unlike targeting moieties limited to specific cancers, WZB117 offers broader therapeutic potential, making it a valuable candidate for a universal targeting strategy. Liposomes were selected as the nanocarriers, and calcein was used as the model drug due to its traceable fluorescent properties. To enable cancer-specific targeting, WZB117 was incorporated as a surface moiety, leveraging elevated glucose uptake in malignant cells. Release performance was evaluated at ultrasound power densities of 6.2, 9, and 10 mW/cm² to assess the effect of acoustic intensity, and three kinetic models were applied to understand the release mechanism. Characterization confirmed successful liposome preparation. Dynamic Light Scattering showed that both control and conjugated liposomes maintained stable particle sizes during the three-month period, with minor fluctuations between 90 and 100 nm. Polydispersity values remained below 0.25, and statistical analysis showed no significant changes (p > 0.05), confirming good colloidal stability. Stewart assay results showed lipid yields of 58.64% for control liposomes and 62.23% for the conjugated formulation, with no statistical difference (p = 0.56), indicating that WZB117 did not alter lipid concentration or structural integrity. FTIR analysis verified successful conjugation through the disappearance of the chlorine peak and the appearance of a new ether bond and characteristic signals of the modified amine group. Ultrasound release studies demonstrated that both control and WZB117-conjugated liposomes were sonosensitive and released their payload upon LFUS exposure. The conjugated liposomes released more slowly and in a more sustained manner, indicating enhanced bilayer stability. Kinetic modeling showed that both formulations best fit the first-order model, consistent with diffusion-controlled behavior. The conjugated liposomes also demonstrated high linearity across the three models, with R² values exceeding 0.97, indicating a uniform and predictable release profile and supporting their potential for more precise cancer therapy.