The project intends to address current deficiencies in cancer therapy by preparing new types of drug delivery vehicles; tiny particles capable of delivering chemotherapeutic agents directly to tumour sites. As most anticancer drugs are unselective in their toxicity – they kill healthy cells as well as cancerous ones – side effects of treatment can be very harmful, including hair loss, kidney damage, long term sickness, etc. If the active compound can be encapsulated in a targeted carrier, then it will not interact with healthy cells as it travels to the site of disease, where it can release the drug and destroy the cancer. This concept of drug delivery promises to reduce the dose of drugs required, mitigate harmful side effects, and also widen the range of drugs that can be used, in particular allowing unstable or poorly soluble drugs to access disease. The project is developing a class of materials known as metal-organic frameworks (MOFs) for drug delivery. MOFs are network solids composed of metal nodes and organic linkers, which, on the molecular scale, resemble grids or meshes. The structures have significant empty space in their interiors, and so can absorb remarkable quantities of molecules such as drugs, and can be thought of as “nanosponges”. MOFs are ideal for drug delivery, as they have high loading capacities for drugs, and can dissociate in the body into their respective components which can be completely non-toxic. Our project seeks to develop methods to control particle size, as drug delivery agents need to be <150 nm (i.e. nanoparticles) in size to avoid blocking veins and capillaries in the body, and to control their surface chemistry, which will allow tuning of stability, incorporation of targeting functionality to direct the MOFs to specific tumours and machinery to allow release of the drug upon response to stimuli found only in cancerous cells. Our objectives are development of new methodology to control synthesis of MOFs and their size and surface chemistry, interfacing of MOFs with biomolecules such as peptides and DNA to provide targeting properties and “stealth” protection towards enzymatic degradation, incorporation of molecular machines to control drug loading and release, and using the inherent properties of the metals that link the MOFs for imaging (e.g. MRI) to allow simultaneous monitoring and treatment of cancers. The project is clearly important for society, as >1/3 of the world’s population will receive treatment for cancer in their lifetime. Any improvement in treatment efficiency or reduction in side effects will have great impact on the health of the world’s population. Additionally, the fundamental information gained from the project could influence other proposed applications of MOFs in carbon dioxide capture and green energy, to name only two, which are pressing societal problems.
