Acoustically activated release of estrone-targeted liposomes used for breast cancer treatment

A Master of Science thesis in Chemical Engineering by Najla Mohammad entitled, "Acoustically activated release of estrone-targeted liposomes used for breast cancer treatment," submitted in January 2016. Thesis advisor is Dr. Ghaleb Al Husseini. Soft and hard copy available.

Abstract

Chemotherapy is frequently used in cancer treatment. However, side effects associated with this type of treatment are often detrimental to the patient's health. This thesis discusses a novel approach of delivering a cytotoxic drug to tumor without affecting adjacent healthy tissues, thus minimizing the adverse side effects of conventional chemotherapy. Liposomes are nanocarriers used to encapsulate and deliver certain cytotoxic agents (e.g., doxorubicin) to malignant cells. Moieties can be attached to the liposome surface to target them to specific cancer cells, by interaction with specific cell membrane receptors. Once there, a stimulus, such as ultrasound can be used as a trigger to release the drug from these nanovehicles. In this study, estrone-targeted and non-targeted liposomes, encapsulating the model drug calcein, were synthesized. Estrone-targeted liposomes are promising delivery vehicles for breast cancer treatment, since most breast cancer cells overexpress receptors for this hormone. The sizes of the liposomes were determined by dynamic light scattering, and both were characterized as large unilamellar vesicles, with non-significant differences between them. The release from the synthesized liposomes triggered by ultrasound waves at low frequency (20 kHz) and high frequency (1.07 and 3.24 MHz), at several power densities, was determined by monitoring the changes in calcein fluorescence, using a spectrofluorometer. The final release at low frequency did not show a significant difference between both types of liposomes, when compared at the same power density, but the initial release rate, measured as the fluorescence increase after the first US pulses at 6.08 and 11.83 W/cm2 power densities, was significantly higher for targeted liposomes. Increasing power densities showed a significant effect on release for both types of liposomes during the first two US pulses, but the final release for non-targeted liposomes showed a different response to power density as compared to targeted liposomes. Finally, the release for higher frequencies significantly increased with increasing power density, for both liposome type, but did not show a significant difference when both types were compared at the same power density and frequency.