Cytosolic delivery of membrane-impermeable molecules in dendritic cells using pH-Responsive core-shell nanoparticles

Abstract

Polycations that absorb protons in response to the acidification of endosomes can theoretically disrupt these vesicles via the ``proton sponge'' effect. To exploit this mechanism, we created nanoparticies with a segregated core-shell structure for efficient, noncytotoxic intracellular drug delivery. Cross-linked polymer nanoparticies were synthesized with a pH-responsive core and hydrophilic charged shell designed to disrupt endosomes and mediate drug/cell binding, respectively. By sequestering the relatively hydrophobic pH-responsive core component within a more hydrophilic pH-insensitive shell, nontoxic delivery of small molecules and proteins to the cytosol was achieved in dendritic cells, a key cell type of interest in the context of vaccines and immunotherapy.