Metal Phenolic Network Nanoparticles as Modular Platforms for Targeted Drug Delivery and Medical Imaging of the Innate Immune System

The project aims to create nanoparticular drug delivery vehicles from metal phenolic networks (MPNs). These are coordination compounds formed from a phenolic group such as tannic acid, and a metal ion, such as iron(III). These MPNs are capped by a polymeric molecule to form spherical nanoparticles and control particle size. The capping group currently being used is synthesised hyaluronic acid modified with dopamine. This is to introduce a metal chelator that can bind via coordination to the metal ion. Finally, a small drug molecule such as Doxorubicin or Curcumin with metal coordination functional groups can be encapsulated into the network. Later they can be released at the target site in the body when particle dissociation occurs.
The nanoparticle surfaces can be functionalised using a targeting molecule, enabling the particle to accumulate at a targeted therapeutic site, for example a cancerous tumour, rather than being distributed and metabolised throughout the body. By using this approach, the treatment becomes more efficacious and reduces side effects as only diseased cells are targeted as opposed to healthy ones.
The particles can be labelled with radioactive metal isotopes to enable medical imaging such as PET scanning. Currently, medical imaging has low resolution and surgical outcomes can be poor if the imaging is not accurate. By using targeted imaging agents, this can be avoided. Finally, the nanoparticles are being synthesised via a flash nanocomplexation method, which has involved the design and production of a flow mixer called a multi-vortex inlet mixer (MVIM), which improves the scalability, uniformity and size distribution of the particles.
The particles are being adapted for targeting towards the innate immune system. This is achieved by creating a particle size that is selectively taken up and digested by immune cells and delivered to the bone marrow, liver and spleen, releasing a small molecule which can activate or deactivate signalling path