期刊
BIOMACROMOLECULES
卷 10, 期 4, 页码 756-765出版社
AMER CHEMICAL SOC
DOI: 10.1021/bm801199z
关键词
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资金
- Institute of Soldier Nanotechnology, [DAAD19-02-D-0002]
- Human Frontier Science Program, and the National Science Foundation [0348259]
- NIH [CAI 12967, CAI 19349]
- Howard Hughes Medical Institute.
- National Science and Engineering Research Council of Canada
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [0348259] Funding Source: National Science Foundation
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.
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