University of Twente Student Theses


Drug targeting inflammatory macrophages in the synovial membrane using VHH coated LNPs

Fakkert, R.W.M. (2023) Drug targeting inflammatory macrophages in the synovial membrane using VHH coated LNPs.

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Abstract:Synovitis is the inflammation of the synovial membrane and is present in joint diseases like osteoarthritis (OA) and rheumatoid arthritis (RA), in which macrophages play an important role. Activation of the different types of macrophages is a factor in the severity of OA and RA. Because of this, drugs that can target macrophages could be used to develop therapies that slow down the progression and/or stimulate regeneration. Molecules that can influence the behaviour of macrophages are nucleic acids like mRNA. A way to encapsulate and transport mRNA is by using ionizable lipid nanoparticles. When these ionizable LNPs are released in the body, they are neutral at physiological pH. If taken up by a cell in an endosome, the low pH causes the LNPs to become cationic, after which they are broken down and can release their content. However, for targeting specific types of macrophages only, the LNPs are coated with VHHs. These are antibody fragments that have almost the same binding characteristics as normal antibodies but are way smaller. In this research, we try to make LNPs that have VHHs conjugated to them. As a proof of concept, we make LNPs that contain DNA and are conjugated with TNFα-specific VHHs.
Item Type:Essay (Bachelor)
Faculty:TNW: Science and Technology
Subject:44 medicine
Programme:Biomedical Technology BSc (56226)
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