Medizinische Universität Graz - Research portal
Selected Publication:
Frascione, D.
Liposomal Contrast Agents for the Diagnosis of Atherosclerotic Plaques
PhD-Studium (Doctor rerum naturalium); DS Molekularbiologie und Biochemie; [ Dissertation ] NAWI Graz; 2012. pp.176.
- Authors Med Uni Graz:
- Advisor:
- Prassl Ruth
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- Abstract:
- In my thesis, sterically stabilized magnetic liposomes (sMLs) containing both a high payload of ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) and fluorescent dyes were designed, synthesized and characterized. Multiple labeling of sMLs enabled us to visualize the nanoconstructs by both fluorescence- and magnetic resonance imaging (MRI). As magnetic nanoparticles we have tested two different commercially available surface-coated USPIOs. The synthesized sMLs were compared in terms of magnetization and colloidal stability. Average diameter size, morphology, encapsulation efficiency and magnetic behavior of sMLs in agarose gel phantoms were investigated. The in vivo pharmacokinetics of sMLs in control mice was also assessed. We could demonstrate that the physicochemical characteristics of the nanocores play an important role on the development of sMLs. For the recognition of atherosclerosis (AS), two biomarkers (BMs) involved in the AS-scenario were coupled to the multifunctional sMLs. As BMs we used either the globular domain of the adipocytokine Adiponectin (gAd) or the anti-inflammatory cytokine Interleukin 10 (IL10). We could show, in an Apolipoprotein E-/- mouse model for AS, that both gAd- and IL10-sMLs were able to target AS-plaques in vivo. This result was visualized ex vivo by confocal laser-scanning microscopy (CLSM). In a rabbit model for AS, MRI quantitative analysis revealed that sMLs and gAd-sMLs produced a stronger signal reduction of AS-regions compared to the free USPIOs. sMLs are, therefore, considered promising contrast agents for molecular MRI and they can be potentially used for testing new targeted strategies in cardiovascular medicine.