pH-Responsive Transferrin-pHlexi Particles Capable of Targeting Cells in Vitro

Targeting nanoparticles to specific cellular receptors has the potential to deliver therapeutic compounds to target sites while minimizing side effects. To this end, we have conjugated a targeting protein, holo-transferrin (holo-Tf), to pH-responsive polymers, poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) and poly(2-(diethylamino)ethyl methacrylate)-ran-poly(2-(diisopropylamino)ethyl methacrylate (PDEAEMA-r-PDPAEMA). These protein-polymer hybrid materials were observed to self-assemble when the pH is increased above the pK_a of the polymer. We demonstrate that their response to pH could be tuned depending on the polymer constituent attached to holo-Tf. Importantly, the targeting behavior of these nanoparticles could be maximized by tuning the density of holo-Tf on the nanoparticle surface by the introduction of a (PDEAEMA-r-PDPAEMA)-b-poly(ethylene glycol) (PEG) copolymer.