Journal
NANO LETTERS
Volume 7, Issue 10, Pages 3056-3064Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nl071542i
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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 nanoparticles with a segregated core-shell structure for efficient, noncytotoxic intracellular drug delivery. Cross-linked polymer nanoparticles 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.
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