Vaccination and targeted therapy using liposomes : opportunities for treatment of atherosclerosis and cancer

Benne, N. (2020)

Doctoral Thesis

This thesis focuses on using liposomes in two different treatment strategies; vaccination (or immunotherapy) and delivery of a small molecule, and in two different disease models; cancer and atherosclerosis. For each of these treatment strategies, the liposomal formulation was tailored to obtain the desired therapeutic effect. Chapter 2 reviews some of the most important physicochemical properties (size, shape, and rigidity) that determine the immunological effects of liposomes and other nanoparticles. In chapter 3 we present a detailed study on the effect of the rigidity of anionic liposomes, as measured by atomic force microscopy, on antigen-specific regulatory T-cell (Treg) responses. In chapter 4, we show that our optimized anionic liposomes can induce potent antigen-specific Treg responses, and can be used to delay atherosclerosis progression in a mouse model. Chapter 5 also focuses on liposomal treatment of atherosclerosis, but here targeted liposomes were prepared to successfully deliver a small molecule to foam cells in atherosclerotic plaques. In Chapter 6, we used cationic liposomes in combination with an adjuvant for cancer immunotherapy in mice. Finally, we summarize the overall findings in chapter 7 and discuss perspectives of using liposomes for vaccination and targeted drug delivery.

• Vaccination
• Liposomes
• Atherosclerosis
• Atomic force microscopy
• Rigidity
• Tolerance
• Immunotherapy
• Lyp-1
• Foam cells
• Liver X Receptor Agonist

• All authors: Benne, N.
• Supervisor: Jiskoot W., Kuiper J.
• Co-supervisor: Slütter, B.A.
• Committee: Irth, H.; Bouwstra, J.A.; Mastrobattista, E.; Perrie, Y.; Eden, W. van
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden Academic Centre for Drug Research (LACDR), Faculty of Science, Leiden University
• Date: 2020-09-08
• ISBN (print): 9789463759465