Next-generation protein-nanoparticle conjugates through the oriented installation of proteins on precision engineered nanoparticles for targeted medic

Target-specific imaging agents (based on nanoparticles) have the potential to overcome traditional issues in Summary.medical imaging: fast clearance leading to poor image enhancement, and the high doses that are often used to surmount this frequently cause negative patient side-effects. The successful development of targeted nanoscaffolds is contingent upon the conjugation of nanoparticles to target-specific ligands, especially protein-based ligands. Whilst technologies for the fusion of nanoparticles to proteins exist, their chemistry is limited in that currently there is little control over how the protein is attached to the nanoparticles and it often uses unstable non-covalent interactions - leading to poor reproducibility of results, stability issues in serum and suboptimal binding to cell surfaces. Herein, we will initially seek to target colorectal cancer, the 4th most common cancer in the UK and 2nd leading cause of cancer-related death in western societies.
In this project, we will initiate a new interdisciplinary collaboration using the expertise of the VC group in site-selective protein modification of clinically relevant scaffolds and the GLD group in nanoparticulate medical imaging agents. This new partnership will make possible the precise installation of functional groups on magnetic resonance imaging (MRI) active nanoparticles, where the density of available conjugation sites on the surface can be controlled to create high-level protein-nanoparticle conjugates which are capable of targeting specific disease sites.
Overall, we aim to create a method which enables the covalent and precise installation of targeting proteins to nanoparticle surfaces; a highly sought after unmet need in the field. We will leverage the medical expertise of both investigators to develop a state of the art medical imaging conjugate in the area of colorectal cancer, where clinically relevant protein/antibodies have been identified (e.g. colon cancer secreted protein 2, CCSP-2). This work aligns very closely with the UCL CDT applications in "Chemistry of Light/Molecule interactions" and "Atoms to Innovations", and the EPSRC Healthcare Technologies call.