Molecularly engineered iron-catalysed cancer nanomedicine

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Cancer immunotherapy is revolutionizing cancer treatment. However, the current immunotherapy drugs, which target immune checkpoint blockade using monoclonal antibodies (mAb), only benefit a relatively small fraction of cancer patients, and the treatments are extremely expensive. Nanotechnology, chemical science approaches and advanced biomaterials will play a critical role in the development of more effective immunotherapy treatments that can help more patients. One of the promising areas is in the development of small-molecule inhibitors of immune checkpoints but these efforts are still in early stages. mAb-based immune checkpoint inhibitors targeted to the Programmed Cell Death-1/Programmed Cell Death-Ligand 1 Signalling Pathway have been particularly effective in clinical trials. However, specific delivery of the drugs to the tumour microenvironment (TME) and modulating the immunosuppressive TME to improve the response to the therapy is very challenging. Nanomaterials are uniquely suited to overcome these challenges as they can be rationally designed to act as drug delivery vehicle and to trigger additional anti-tumour responses. This PhD project will harness a versatile platform technology that encapsulating iron oxide nanoparticles inside phospholipid micelles (mIONPs) enables effective in vitro and in vivo delivery of the anti-cancer drugs to the tumour cells. The construct provides imaging and magnetic features to locate, guide and study cellular specificity and biodistribution and therapeutic responses. In this construct intrinsic cancer therapy is also provided by its iron content and enzyme-like properties.The PhD project seeks to develop new molecular tools (small-molecules and iron nanostructured materials), bioorthogonal catalysis and bioconjugation protocols to create an innovative chemoimmunotherapeutic iron-loaded lipid nanoparticle. The construct will have chemically programmed features for immune checkpoint blockade targeting the PD-1/PD-L1 pathway, with the potential to overcome immune-suppression in the TME and to trigger iron-catalysed cancer cell death. Ultimately, the goal is creating a nanomedicine platform that significantly improves current immunotherapy and chemoimmunotherapy, and with potential for translation into clinical practice.