Hydrogel-Induced Cell Membrane Disruptions Enable Direct Cytosolic Delivery of Membrane-Impermeable Cargo.

Autor: Van Hoeck J; Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium., Van de Vyver T; Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium., Harizaj A; Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium., Goetgeluk G; Department of Diagnostic Sciences, Ghent University, Corneel Heymanslaan 10, Ghent, 9000, Belgium., Merckx P; Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium., Liu J; Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium., Wels M; Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium., Sauvage F; Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium., De Keersmaecker H; Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium.; Centre for Advanced Light Microscopy, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium., Vanhove C; Infinity Lab, Medical Imaging and Signal Processing Group-IBiTech, Faculty of Engineering and Architecture, Ghent University, Corneel Heymanslaan 10, Ghent, 9000, Belgium., de Jong OG; CDL Research, Division LAB, UMC Utrecht, Faculty of Medicine, Utrecht University, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands.; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Science, Utrecht University, Universiteitsweg 99, Utrecht, 3584 CG, The Netherlands., Vader P; CDL Research, Division LAB, UMC Utrecht, Faculty of Medicine, Utrecht University, Heidelberglaan 100, Utrecht, 3584 CX, The Netherlands., Dewitte H; Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium., Vandekerckhove B; Department of Diagnostic Sciences, Ghent University, Corneel Heymanslaan 10, Ghent, 9000, Belgium., Braeckmans K; Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium.; Centre for Advanced Light Microscopy, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium., De Smedt SC; Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium.; Centre for Advanced Light Microscopy, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium., Raemdonck K; Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent, 9000, Belgium.
Jazyk: angličtina
Zdroj: Advanced materials (Deerfield Beach, Fla.) [Adv Mater] 2021 Jul; Vol. 33 (30), pp. e2008054. Date of Electronic Publication: 2021 Jun 09.
DOI: 10.1002/adma.202008054
Abstrakt: 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 T 1 -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.
(© 2021 Wiley-VCH GmbH.)
Databáze: MEDLINE
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