Designing chemokine-loaded temperature-sensitive liposomes
Rubio, Angel Jonathan
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Surgery, radiation, and chemotherapy have been the primary options for cancer patients; however, the recent emergence of immunotherapy has revolutionized the cancer treatment paradigm. Cancer immunotherapies employ a patient’s immune system to recognize and fight cancer, but recruiting immune cells to tumors specifically and in adequate numbers is a significant challenge. Therefore, the goal of this thesis was to develop a technology that was capable of directing immune cell migration in an effort to promote antitumor immunity and combat cancer growth. Specifically, we have packaged chemokines, signaling proteins that promote immune cell migration, inside temperature-sensitive liposomes (TSLs). These nanocarriers are capable of being thermally triggered to enable selective localized release of encapsulated chemokines at the tumor site and have shown previous success for delivery of conventional chemotherapies. For the initial step in the design of the chemokine-loaded TSLs, multiple chemokines were investigated to select an optimal immune cell recruitment profile. Furthermore, we have designed a novel liposomal composition to ensure sufficient stability and temperature-sensitive chemokine release. The TSLs were shown to be capable of releasing chemokines to promote immune cell recruitment. Additionally, the TSLs were shown in vitro to limit cancer cell growth by increasing immune cell recruitment. The administration of the chemokine in a mice tumor model demonstrated its ability to delay tumor growth and result in smaller tumors. This strategy of encapsulating chemokines within TSLs paves the way for additional cancer immunotherapies and chemokine-based therapies.