Biomimetic Hetero-Multivalent Binding Nanoparticles for Cell Recognition

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One of the fundamentally attractive properties of nanomaterials is their ability to serve as drug carriers. They can deliver drugs to sites of action that these would not be able to reach based on their physicochemical properties. However, a fundamental problem involved with this strategy is the specificity of recognizing the target cells. Even though a number of principles of nanomaterial interactions with cells have been described in the literature, they hardly allow a nanomaterial to distinguish between the target- and off-target cells that it may have contact to on its way through the organism. Viruses in contrast, which are essentially nanoparticles too, have developed highly sophisticated techniques to cope with the problem of target cell identification. They use several different types of ligands that bind one after another to receptors on the cell surface to confirm its identity. Goal of this project will be to implement this type of biomimetic hetero-multivalent binding in synthetic nanomaterials. We will work on two design strategies. The first will make use of polyethylene glycol tethers of different length to arrange for a delayed visibility of two receptor ligands on the nanoparticle surface. The second rests on the initial recognition of a cell by a ligand and the confirmation of the cell's identity by its ability to activate a proligand on the nanoparticle surface enzymatically. The ultimate goal will be to obtain particles that are internalized exclusively by their target cells. Mesangial cells will serve as therapeutic target. They are responsible for fibrotic processes during diabetic nephropathy the leading cause of end-stage kidney disease. The project is intended to explore the potential of biomimetic particles as a drug carrier for treating a disease for which therapeutic options are hardly available.