ENGINEERING NANOPARTICLE-WATER COUPLING; ionic, hypoxic, logic and molecular contrast switches

Ziel

The fundamental objective of the research described in this proposal is to establish foundations for controlling the interactions between magnetically-active inorganic centres and the molecular water around them. Magnetic centres, paramagnetic complexes or ferromagnetic cores, are capable of generating high-levels of MRI contrast in a manner highly reflective of these interactions. The shrouding of these in functional organic dielectrics/biologically-mimicking membranes enables a “gating” of water interactions such that they are turned on/primed to turn on under very specific conditions. This project will seek to engineer this control within diffusively-mobile nanoparticle constructs such that they are responsive to specific ions, local pH or hypoxic conditions, indicative of disease. A central part of the work will focus on controlling water flux across artificial bilayers in a manner akin to the bilayer controls that support life (where, for example, proton transmembrane flux underpins respiration). A second strand will focus on gating water access by triggering changes in polymer wettability. Inorganic magnets wrapped in membranes will also present a plug and plug platform where zwitterionic and integrated antibody densities can be optimised to maximise the specificity and selectivity of targetting. The outer surfaces of these bilayer-wrapped ferromagnetic particles will be hydrated; the binding of a target will displace this and thus reduce the volume of water that interacting with the magnetic field generated by the inorganic core (leading to another new MRI sensing platform). The fact that these ferromagnetic cores can be precisely manipulated by electromagnetic fields will be utilised in shaking particles controllably with low blood volumes and optimising the capture of rare targets; this will be applied herein to underpin a step change in our ability to capture circulating tumour cells and diagnose presymptomatic Parkinson's.