Hyperbranched polymers and other nanoparticles to probe immune cell interactions

Project Summary

As a model to investigate these interactions CBNS researchers are using well-defined nanomaterials known as hyperbranched polymers.

Surface charge was an initial focus of this investigation since they are the dominant physical parameters that dictate the route (absorption, distribution, metabolism and excretion) of polymeric nanocarriers in the human body and whether they can by-pass the numerous biological barriers or obstacles and take effect at the desire locations.

The HBPs were evaluated for activation of human immune cells and were found to have a charge- dependent activation of dendritic cells, which are responsible for the immune response to vaccines and pathogens.

Positively charged HBPs activated a major dendritic cell subset within human blood, while neutral and negatively charged HBPs had no immuno-stimulatory effect. Moreover, charge dictated their association with different immune cell subsets.

At physiological temperatures, all cell types associated with positively charged HBPs, while negatively charged HBPs selectively associated with cells specialised for pathogen clearance and processing.

Reducing non-specific uptake of nanoparticles is essential for the development of effective drug delivery systems. In one study, we investigated how the surface chemistry of nanoparticles (linear or branched PEG molecules) can be modified to reduce non-specific clearance in human blood.

In other work, we modified the surface of star polymers (small nanoparticles with drug delivery and imaging potential) to interact with reactive groups (thiols) found on the outer surface of certain cancer and some immune cells.

We have demonstrated that thiol-reactive star polymers showed increased association with cancer cells and some key cell types of human blood (dendritic cells, B cells and platelets). This represents a non-conventional (i.e. non-antibody) method of targeting small nanoparticles to cells and may lead to improved drug delivery and imaging capabilities.

These studies provide us with strategies to predict and evaluate the fate of polymers at whole body and cellular levels, making the application of polymeric materials in vaccine delivery more time and cost effective.