Targeting HER2-positive cancer using multifunctional nanoparticles

Christian Ammitzbøll Juul

    Research output: Book/ReportPh.D. thesisResearch

    Abstract

    Advanced delivery of chemotherapeutics to tumor tissue is an active field of research, as it offers several benefits over conventional cancer therapies. In the three introductory chapters of this thesis, the development of liposomes as drug carriers, including novel strategies to improve delivery efficiency, is thoroughly reviewed.
    Chapter 4 encompasses a comprehensive manuscript, which describes the in vitro and in vivo evaluation of a novel liposomal delivery platform designed to target the HER2 receptor on cancer cells and be activated by enzyme activity in the tumor.
    In Chapter 5, an alternative HER2-targeted liposome formulation was assessed in vitro. Rather than being enzyme-sensitive, these liposomes were responsive to reducing conditions. Such conditions are found in several cancers due to hypoxia as well as in endocytic compartments.
    The progressive in vitro optimization of a complex multifunctional liposomal formulation is reviewed in Chapter 6. This formulation is similar to the one described in Chapter 4, but the lipid composition of the liposomes has been changed to make the formulation sensitive to low pH and prone to engage in advantageous interactions with other lipid membranes.
    The final study, described in Chapter 7, comprises an in vivo evaluation of the potential benefits of combining enzyme-sensitive liposomal oxaliplatin with the HER2-targeted antibody trastuzumab.
    As concluded in the final comments in Chapter 8, the extensive in vitro and in vivo data reported in this thesis demonstrate the potential of using HER2-targeting in combination with advanced drug release mechanisms and present exciting new perspectives for the development of novel delivery platforms.
    Original languageEnglish
    PublisherDTU Nanotech
    Number of pages138
    Publication statusPublished - 2016

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