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Cytosolic Delivery Mediated via Electrostatic Surface Binding of Protein, Virus, or siRNA Cargos to pH-Responsive Core−Shell Gel Particles
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    Cytosolic Delivery Mediated via Electrostatic Surface Binding of Protein, Virus, or siRNA Cargos to pH-Responsive Core−Shell Gel Particles
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    Departments of Chemical Engineering, Biology, Biological Engineering, and Materials Science and Engineering, Koch Institute for Integrative Cancer Research, and Howard Hughes Medical Institute, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139
    * To whom correspondence should be addressed. Tel.: 617-452-4174. Fax: 617-452-3293. E-mail [email protected]
    †Department of Chemical Engineering.
    ‡Koch Institute for Integrative Cancer Research.
    §Department of Biology.
    ∥Department of Biological Engineering.
    ⊥Department of Materials Science and Engineering.
    #Howard Hughes Medical Institute.
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    Biomacromolecules

    Cite this: Biomacromolecules 2009, 10, 4, 756–765
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    https://doi.org/10.1021/bm801199z
    Published February 25, 2009
    Copyright © 2009 American Chemical Society

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    We recently described a strategy for intracellular delivery of macromolecules, utilizing pH-responsive “core−shell” structured gel particles. These cross-linked hydrogel particles disrupt endosomes with low toxicity by virtue of physical sequestration of an endosome-disrupting “proton sponge” core inside a nontoxic hydrophilic shell. Here we tested the efficacy of this system for cytosolic delivery of a broad range of macromolecular cargos, and demonstrate the delivery of proteins, whole viral particles, or siRNA oligonucleotides into the cytosol of dendritic cells and epithelial cells via core−shell particles. We assessed the functional impact of particle delivery for vaccine applications and found that cytosolic delivery of protein antigens in dendritic cells via the core−shell particles promotes priming of CD8+ T-cells at 100-fold lower doses than soluble protein. Functional gene knockdown following delivery of siRNA using the particles was demonstrated in epithelial cells. Based on these findings, these materials may be of interest for a broad range of biomedical applications.

    Copyright © 2009 American Chemical Society

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    Biomacromolecules

    Cite this: Biomacromolecules 2009, 10, 4, 756–765
    Click to copy citationCitation copied!
    https://doi.org/10.1021/bm801199z
    Published February 25, 2009
    Copyright © 2009 American Chemical Society

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