The development of next-generation nanoparticle delivery systems using variable new antigen receptors for the treatment of cancer

Possessing remarkable stability, far superior to that of antibodies or fragments and an ability to bind cryptic/hidden epitopes with high affinity, it is hypothesised that vNARs may be ideally suited not only to inhibiting the activity of these intracellular antigens, but as promising alternatives to monoclonal antibodies in targeting cell surface proteins. <br> <br>One of the most pertinent challenges affecting drug development, is the ability to control the biological fate of the active pharmaceutical ingredient (API) following administration.

Therefore, this thesis illustrates the isolation and evaluation of novel vNAR binders towards a panel of both intracellular and extracellular targets for application in the treatment of cancer. Isolated vNARs were evaluated for development into a novel vNAR-conjugated, nanoparticle-based delivery systems for superior delivery of cytotoxic payloads. Alongside this, a cationic nanoparticle delivery system was developed to facilitate enhanced cellular uptake and intracellular cargo delivery.<br><br><i>Thesis embargoed until 31 July 2027</i>.<br>