Cytosolic Delivery of Membrane-Impermeable Molecules in Dendritic Cells Using pH-Responsive Core?Shell Nanoparticles

阅读量:

89

作者:

Y HuT LitwinAR NagarajaB KwongJ KatzN WatsonDJ Irvine

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摘要:

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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DOI:

10.1021/nl071542i

被引量:

448

年份:

2007

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