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. 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.
Hu
Yuhua
Y
Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Litwin
Tamara
T
Nagaraja
Arpun R
AR
Kwong
Brandon
B
Katz
Joshua
J
Watson
Nicki
N
Irvine
Darrell J
DJ
D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology; D002463:Cell Membrane Permeability / Q000502:physiology; D003460:Crystallization / Q000379:methods; D003600:Cytosol / Q000737:chemistry*; D003713:Dendritic Cells / Q000737:chemistry* / Q000502:physiology*; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000502:physiology*; D046911:Macromolecular Substances / Q000737:chemistry; D008422:Materials Testing; D008968:Molecular Conformation; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology / Q000379:methods; D010316:Particle Size; D013499:Surface Properties
D046911:Macromolecular Substances