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... Show moreThis 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. Show less
Atherosclerosis is a chronic inflammatory disease of the vasculature in which both a disturbed lipid metabolism and inflammatory immune responses against several self-antigens are involved. In this... Show moreAtherosclerosis is a chronic inflammatory disease of the vasculature in which both a disturbed lipid metabolism and inflammatory immune responses against several self-antigens are involved. In this thesis we have explored the effectiveness of DC-immunotherapy in atherosclerosis. We have used different strategies to target the immune component in different stages of atherosclerosis. First we used DCs as a vaccination strategy to induce a protective antibody response trough the injection of oxLDL-pulsed DCs or to target NKT cells by the injection of OCH-pulsed DCs. Next we assessed the potential of DC-immunotherapy in a model of established atherosclerosis. We also evaluated the effects of a disturbed TGF-_ signaling in DCs and the subsequent effects on atherosclerosis by using ApoE-/- which have a dysfunctional TGF-__ Receptor II under the CD11c promoter. Next, we were interested in the effect of foam-cell formation on the antigen-presenting capacity of DCs and macrophages. Therefore we studied the effect of oxLDL-loading on antigen uptake and antigen presentation by DCs and macrophages. Finally, by depleting or inducing Tregs we investigated the potential role of regulatory T cells in a mouse model for aneurysm formation. Show less
