Stimulus-Responsive Reversible Pegylation of Nanocarriers

Drug delivery approaches using nanocarriers often rely on active or passive targeting techniques to enhance the therapeutic outcome and reduce off-target effects. To ensure accumulation at the targeted site a long circulation time in the blood is needed. Coating of nanoparticles with PEG or other polymers is an established method to achieve this goal. The coating reduces the clearance of the particles by the Mononuclear Phagocyte System (MPS) by reducing the interaction with serum proteins. The downside of the coating is that the nanocarriers suffer from slow drug release and reduced endocytosis once they have reached their target. A reversible coating of nanocarriers allows combining long circulation times with high drug release/cell interaction at the target site.

The aim of this study was to engineer a nanocarrier with stimulus-controlled reversible PEGylation.

For the generation of such a nanocarrier the diagnostic agent fluorescein was immobilized on the surface of a nanocarrier. In addition, an antibody fragment (scFv) against fluorescein was highly PEGylated at multiple residues. The binding of the PEGylated scFv to the nanocarrier-bound fluorescein prevents the uptake by human macrophages. Upon addition of free fluorescein which competes with the binding of the scFv, the protective coat is released resulting in an increased uptake of liposomes by the macrophages.

We could show that the protective coating of a nanocarrier can be controlled by a small molecule inducer. The nanocarrier is able to switch in from a protected to a cell-interacting state. This allows a higher control of the vehicle and could provide a better therapeutic outcome.