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 p K 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.