Nanomedicines designed for intracellular targeting
Nanomedicine, i.e. the application of nanomaterials to clinical medicine, is currently revolutionising health care world-wide: it provides previously undreamt-of tools for the detection, diagnosis, targeting and treatment of diseases. The pathway to this revolution is the development of technologies driven by medical need, but underpinned by an understanding of the fundamental science at the interface of engineered materials and biological systems, and translated by the design of delivery systems and devices that can exploit this understanding. The aim of this project is to develop soft nanoparticles that deliver therapeutics under specific intracellular stimulus. These have been intelligently designed for enhanced cell uptake and are able to release a hydrophobic drug specifically in the endosome, late endosome or lysosome. G Protein Coupled Receptor (GPCR) signaling mediates diverse and cell specific effects related to inflammation, proliferation, anti-apoptosis of cells. In particular, subcellular compartmentalized signaling leads to diverse effects and has been associated with sustained activation of inflammatory signals.
More specifically, trafficked GPCRs into endosomal compartments have been shown to transmit unique signals with distinct outcomes , and thus targeting antagonists to GPCRs in the early or late endosome or lysosome could allow for more selective antagonism with fewer side effects.In this project the candidate will gain experience in advanced polymerisation and materials characterisation techniques, cell cytotoxicity assays, imaging techniques including confocal microscopy and trans mission electron micrscopy. 1.Neurokinin 1 receptor signaling in endosomes mediates sustained nociception and is a viable therapeutic target for prolonged pain relief, Science Translational Medicine 9 (392) ASAP (2017)