Stealth PEG particles for improved in vivo circulation and targeting

Project Summary

The successful delivery of therapeutics or vaccines at the relevant target sites is heavily influenced by biological interactions, for example, the nonspecific uptake of drug carriers by the phagocytic cells of the immune system.

Modifying the surface of nanoparticle drug carriers with polyethylene glycol (‘PEGylation’), has been the most widely used strategy to reduce non-specific clearance and to prolong circulating lifetimes. However, PEGylation is usually dependent on the PEG chain architecture and PEG surface density, both of which are difficult to finely control and simulate.

CBNS researchers circumvented the issues relating to PEG chain architecture and PEG density on the surface of particles and instead engineered particles composed entirely of PEG by infiltrating PEG into mesoporous silica templates.2,3 They also improved in vivo circulation times of the PEG particles by modifying the molecular weight, size and rigidity of the PEG polymer.

We have initiated another three-way collaboration amongst CBNS Chief Investigators, Professor Frank Caruso (Melbourne), Associate Professor, Kris Thurecht (UQ), and Professor Stephen Kent (Melbourne), where we have prepared our PEG particles with ‘bispecific’ antibodies (where one arm of the antibody binds to the PEG and one arm to a desired target). This has been promising for targeting cancer cell lines and we are now testing the same concept to target immune cells in blood.