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

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• 作者：Yuhua Hu ; Tamara Litwin ; Arpun R. Nagaraja ; Brandon Kwong ; Joshua Katz ; Nicki Watson ; Darrell J. Irvine
• 刊名：Nano Letters
• 出版年：2007
• 出版时间：October 2007
• 年：2007
• 卷：7
• 期：10
• 页码：3056 - 3064
• 全文大小：831K
• 年卷期：v.7,no.10(October 2007)
• ISSN：1530-6992

文摘

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 intracellulardrug delivery. Cross-linked polymer nanoparticles were synthesized with a pH-responsive core and hydrophilic charged shell designed todisrupt endosomes and mediate drug/cell binding, respectively. By sequestering the relatively hydrophobic pH-responsive core componentwithin a more hydrophilic pH-insensitive shell, nontoxic delivery of small molecules and proteins to the cytosol was achieved in dendriticcells, a key cell type of interest in the context of vaccines and immunotherapy.