ASSESSMENT OF LONG-TERM EXPOSURE TO NANOBIOMATERIALS AND IMPLANTABLE DEVICES
INTRACELLULAR DISTRIBUTION OF NANOPARTICLES
INTERACTIONS OF COMPLEMENT, INFLAMMASOMES AND ENDOTHELIUM THAT TRIGGER ADVERSE EVENTS
Building upon our expertise in the immunocompatibility of engineered materials, we are supporting the development of novel antiretroviral implants, for HIV, by assessing the compatibility and safety. Additionally, we are developing new assays that better represent the administration site.
The uptake of nanoparticles, loaded with therapeutics, into cells and tissues may result in differential subcellular localisation when compared to unformulated therapeutics. In this work, we are examining the mechanisms of uptake, subcellular localisation, and impact on cellular response.
Buillding upon our previous work on how nanoparticles interact with complement and inflammasomes, we are investigating how these systems may affect the endothelium and trigger advers cardiac events.
INFLUENCE OF EXTRACELLULAR VESICLES ON IMMUNE RESPONSES
DEVELOPMENT OF, BIOCOMPATIBLE, RADIOSENSITISERS FOR CHEMOTHERAPY
REPURPOSING OF EXISITING THERAPIES TO ADDRESS COVID-19 RELATED INFLAMMATION
Extracellular vesicles have been demonstrated to influence immune responses and modulate immune cell activity. We are assessing how exosomes, as well as "tolerosomes" can influence immune response to new therapeutics. In addition to defining a mechanistic understanding, we are also assessing if there is any influence on interindividual varaibility in response to materials.
Inorganic nanoparticles are under investigation for their use as radiosensitisers for applications such as proton beam therapy but are known to activate components of the innate immune system. We are supporting our colleagues in the Chemistry Department (UoL) in their work on the development of these key materials.
We are emplying high throughput immunological assays, and in silico approaches, to repurose small molecules to treat the inflammation observed in COVID-19 that leads to poor outcomes in patients. In collaboration with the Liverpool School of Tropical Medicine, Alder Hey and Great Ormond Street Hospital, we are ensuring that patient benefit is at the forefront of our work.
DEVELOPMENT OF IN VITRO MODELS TO REPLICATE ADMINISTRATION SITES FOR INTRAMUSCULAR AND SUBCUTANEOUS ADMINISTRATION OF THERAPEUTICS
REPOLARISATION OF MACROPHAGES
In collaboration with international colleagues, we are developing new therapies to influence immune regulator proteins, known as caspases, in order to treat inflammationthat underpins a number of diseases.
Cutting across a number of our projects, we are developing and refining a number of in vitro models to better represent the orientation and exposure of patients to parenterally administered therapeutics. As well as modeles representing the GI tract and the endothelium, we are using tetraculture models to explore skin immunobiology for transdermal and subcutaneous administration of therapeutics.
We have a number of projects, examining the mechanisms behond polarisation of macrophages. We are particularly interested in M1 macrophage phenotypes and their infuence on chemo- and radiosensitisers.