Controlling endosomal escape using nanoparticle composition: current progress and future perspectives.

Polymer nanoparticles offer significant benefits for improving delivery of biological therapeutics such as DNA and proteins, as they allow the cargo to be protected until it is delivered to a target cell. However, there are still challenges with achieving efficient delivery to the optimal cellular region. One significant roadblock is escape of nanoparticles from within the endosomal/lysosomal compartments into the cytosol. Here, we review the recent advances in understanding endosomal escape of polymer nanoparticles. We also discuss the current progress on investigating how nanoparticle structure can control endosomal escape. It is important to understand the fundamental biological processes that govern endosomal escape in order to design more effective therapeutic delivery systems.

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 pKa 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.