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Hydrogel-Induced Cell Membrane Disruptions Enable Direct Cytosolic Delivery of Membrane-Impermeable Cargo
- Source :
- Advanced Materials, 33(30), 1. Wiley-VCH Verlag
- Publication Year :
- 2021
-
Abstract
- Intracellular delivery of membrane-impermeable cargo offers unique opportunities for biological research and the development of cell-based therapies. Despite the breadth of available intracellular delivery tools, existing protocols are often suboptimal and alternative approaches that merge delivery efficiency with both biocompatibility, as well as applicability, remain highly sought after. Here, a comprehensive platform is presented that exploits the unique property of cationic hydrogel nanoparticles to transiently disrupt the plasma membrane of cells, allowing direct cytosolic delivery of uncomplexed membrane-impermeable cargo. Using this platform, which is termed Hydrogel-enabled nanoPoration or HyPore, the delivery of fluorescein isothiocyanate (FITC)-dextran macromolecules in various cancer cell lines and primary bovine corneal epithelial cells is convincingly demonstrated. Of note, HyPore demonstrates efficient FITC-dextran delivery in primary human T cells, outperforming state-of-the-art electroporation-mediated delivery. Moreover, the HyPore platform enables cytosolic delivery of functional proteins, including a histone-binding nanobody as well as the enzymes granzyme A and Cre-recombinase. Finally, HyPore-mediated delivery of the MRI contrast agent gadobutrol in primary human T cells significantly improves their T1 -weighted MRI signal intensities compared to electroporation. Taken together, HyPore is proposed as a straightforward, highly versatile, and cost-effective technique for high-throughput, ex vivo manipulation of primary cells and cell lines.
- Subjects :
- protein delivery
Materials science
Cell Membrane Permeability
contrast-enhanced MRI
intracellular delivery
membrane disruption
Cell
Contrast Media
02 engineering and technology
010402 general chemistry
01 natural sciences
Cell therapy
Cell membrane
chemistry.chemical_compound
nanogels
Cytosol
Materials Science(all)
Nanocapsules
medicine
Organometallic Compounds
Animals
Humans
General Materials Science
Fluorescein isothiocyanate
Fluorescent Dyes
Electroporation
Mechanical Engineering
Cell Membrane
Epithelium, Corneal
Proteins
Dextrans
Hydrogels
021001 nanoscience & nanotechnology
0104 chemical sciences
Cell biology
medicine.anatomical_structure
Cross-Linking Reagents
chemistry
Cell culture
Mechanics of Materials
Self-healing hydrogels
Cattle
cell therapy
0210 nano-technology
Intracellular
Fluorescein-5-isothiocyanate
HeLa Cells
Subjects
Details
- ISSN :
- 15214095 and 09359648
- Volume :
- 33
- Issue :
- 30
- Database :
- OpenAIRE
- Journal :
- Advanced materials (Deerfield Beach, Fla.)
- Accession number :
- edsair.doi.dedup.....18d5f34f925ff9210c0eacab72c42b76