A Master of Science thesis in Biomedical Engineering by Nour Majdi AlSawaftah entitled, “The Use of Transferrin and Ultrasound in Cancer Treatment”, submitted in May 2019. Thesis advisor is Dr. Ghaleb Husseini. Soft and hard copy available.
Site-specific drug delivery represents an attractive approach in cancer treatment to reduce the undesirable side-effects of anticancer therapeutics and increase the accumulation of drugs at tumor sites. Surface modification of nanoparticles such as liposomes with targeting moieties specific to the receptors on the surface of tumor cells further improves the selectivity of liposomes, while external triggers such as ultrasound can be used to enhance the release of liposomal contents. In this study, the anticancer activity of PEGylated calcein-loaded liposomes targeted with transferrin (Tf) was evaluated. The sizes of liposomes were measured using dynamic light scattering; control liposomes were found to have an average diameter of 82.70±2.88 nm while transferrin liposomes had an average diameter of 87.54±4.81 nm. The presence of transferrin was established using the bicinchoninic acid (BCA) assay, and the total lipid content was quantified using the Stewart assay. Next, low-frequency ultrasound (LFUS) of 20 kHz at three power densities (7.46, 9.85, and 17.31 mW/cm2) and high-frequency ultrasound (HFUS) at two frequencies (1.07MHz and 3MHz) were used to release the contents of 3 batches of control and transferrin liposomes. For LFUS, the release profiles showed an increase in calcein release with increased power density and that transferrin-conjugated liposomes have a significantly higher release when compared to non-targeted liposomes at all three power densities. In addition, nine drug release kinetics’ models were utilized to model the LFUS release profiles. For both types of liposomes, the best fitting models were Korsmeyer-Peppas, Hixson-Crowell, Weibull and Hopfenberg. With regard to HFUS release; both types of liposomes showed a clear increase in release after each insonation; however, the release at 1.07 MHz was higher than that of 3 MHz even though the power density was higher at 3 MHz. Moreover, the release profile for transferrin liposomes showed a more linear increase with time, and the fraction release values tended to be higher than those obtained for control liposomes for both frequencies. Finally, the results of the in-vitro cell work indicated that Tf-modified liposomes coupled with US were able to enhance the intracellular uptake and cytotoxicity of the entrapped calcein by HeLa cells by around 80.09±30.08% compared to control liposomes.