pH-Responsive Transferrin-pHlexi Particles Capable of Targeting Cells <i>in Vitro</i>

Abstract

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)-<i>ran</i>-poly(2-(diisopropylamino)ethyl methacrylate (PDEAEMA-<i>r</i>-PDPAEMA). These protein-polymer hybrid materials were observed to self-assemble when the pH is increased above the p<i>K</i>_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)-<i>b</i>-poly(ethylene glycol) (PEG) copolymer.