title: Cytosolic delivery of membrane-impermeable molecules in dendritic cells using pH-responsive core-shell nanoparticles.
abstract: 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.
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
authors: Yuhua
authors: Y
authors: Hu
authors: Tamara
authors: T
authors: Litwin
authors: Arpun R
authors: AR
authors: Nagaraja
authors: Brandon
authors: B
authors: Kwong
authors: Joshua
authors: J
authors: Katz
authors: Nicki
authors: N
authors: Watson
authors: Darrell J
authors: DJ
authors: Irvine
mesh_terms: 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
chemical_list: D046911:Macromolecular Substances