Chemical And Nanotechnology-Based Drug Delivery Systems For Cancer Immunotherapy

Immunotherapies for cancer, namely therapies based on the stimulation and manipulation of the immune system's activity against tumour cells, have recently become one of the most promising strategies to provide safer and effective cancer treatment. In particular, the so-called checkpoint-inhibiting immunotherapies have revolutionized the treatment of patients with melanoma and lung cancers. However, cancer immunotherapy is a rapidly expanding field and given the relatively low response rates reported for these treatments and the growing evidence for acquired resistance to immunotherapy in patients, there is now urgent need for new approaches and the development of improved immunotherapy strategies. Although significant progress has been made in nanotechnology-based drug delivery strategies for cancer chemotherapy, the results obtained with these systems in clinical trials have been disappointing. Nevertheless, several features of these drug-delivery platforms could be powerful for developing immunotherapeutic (nano)vaccines. In particular, size and shape control, effective decoration of the drug-delivery platform with active-targeting ligands (i.e. antibodies, peptides, aptamers, cell-specific ligands, etc.) and stimuli-responsive moieties (i.e. responsive to magnetic fields, pH, enzymes, light, ultrasound, etc.) are features capable of improving drug safety and efficacy by triggering on-demand delivery of the therapeutic agents. These features applied to immunotherapy could provide improved control over drug-release profiles, effective cell internalization and intracellular trafficking for targeting both cancer and immune cells at the tumour and tumour-draining lymph nodes to enhance the safety and potency of the immunotherapy treatments.
The objective of this project is the development and optimisation of different nanomaterials for cancer immunotherapeutic purposes, using "smart" chemistry to (bio)functionalise them. The project will design and synthesise high-quality superparamagnetic iron oxide nanoparticles, polymeric nanoparticles and diatom microalgae-derived nanoporous biosilica for improving capture, co-delivery and release of specific adjuvants, antigen peptides (including mutation-associated cancer antigens for personalized therapies) and antibodies. The particle functionalization strategies to be pursued in this project will involve decoration with groups to enable dynamic covalent chemistry and responsiveness to both intracellular environments and tumor microenvironments. The PhD programme will train the student in methods for controlled synthesis, physico-chemical characterization (i.e. size, charge, physiological stability etc.) and functional characterization (i.e. drug-encapsulation and release profiles, 2D and 3D cell culture models systems and multicellular culture in drug discovery, molecular imaging etc.) of the nanoparticles and nanovaccines. This project also aims to identify candidates for potential synergistic treatment combinations capable of enhancing the efficacy immunotherapy through combination and personalized therapies. The project involves collaborating with biologists and clinicians and secondments at the Cancer Immunology Lab in Cardiff, and CIC biomaGUNE and CIQUS in Spain.

EPSRC research area: Chemical biology and biological chemistry.