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

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. C...

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Bibliographic Details
Published in:Nano letters 2007-10, Vol.7 (10), p.3056-3064
Main Authors: Hu, Yuhua, Litwin, Tamara, Nagaraja, Arpun R, Kwong, Brandon, Katz, Joshua, Watson, Nicki, Irvine, Darrell J
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Biotechnology
Cell Line
Cell Membrane - chemistry
Cell Membrane - physiology
Cell Membrane Permeability - physiology
Cross-disciplinary physics: materials science
rheology
Crystallization - methods
Cytosol - chemistry
Dendritic Cells - chemistry
Dendritic Cells - physiology
Drug Delivery Systems - methods
Endocytosis - physiology
Endosomes - physiology
Exact sciences and technology
Fundamental and applied biological sciences. Psychology
Macromolecular Substances - chemistry
Materials science
Materials Testing
Methods of nanofabrication
Methods. Procedures. Technologies
Molecular Conformation
Nanocrystalline materials
Nanoparticles - chemistry
Nanoparticles - ultrastructure
Nanoscale materials and structures: fabrication and characterization
Nanotechnology - methods
Others
Particle Size
Physics
Surface Properties
Various methods and equipments
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Summary: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.
ISSN:1530-6984
1530-6992
DOI:10.1021/nl071542i