Magnetically Guided Protein Transduction by Hybrid Nanogel Chaperones with Iron Oxide Nanoparticles.
Protein pharmaceuticals show great therapeutic promise, but effective intracellular delivery remains challenging. To address the need for efficient protein transduction systems, we used a magnetic nanogel chaperone (MC): a hybrid of a polysaccharide nanogel, a protein carrier with molecular chaperone-like properties, and iron oxide nanoparticles, enabling magnetically guided delivery. The MC complexed with model proteins, such as BSA and insulin, and was not cytotoxic. Cargo proteins were delivered to the target HeLa cell cytosol using a magnetic field to promote movement of the protein complex toward the cells. Delivery was confirmed by fluorescence microscopy and flow cytometry. Delivered β-galactosidase, inactive within the MC complex, became enzymatically active within cells to convert a prodrug. Thus, cargo proteins were released from MC complexes through exchange interactions with cytosolic proteins. The MC is a promising tool for realizing the therapeutic potential of proteins.
Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto, Japan.
Riku
R
Kawasaki
Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto, Japan. sasaki@bio.polym.kyoto-u.ac.jp.
Yoshihiro
Y
Sasaki
Graduate School of Engineering, Hiroshima University, 1-4-1 Kagamiyama, Higashi-Hiroshima, Japan.
Kiyofumi
K
Katagiri
Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto, Japan.|JST-ERATO, Akiyoshi Bio-nanotransporter Project, Kyoto University Katsura, Nishikyo-ku, Kyoto, Japan.
Sada-Atsu
SA
Mukai
Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto, Japan.|JST-ERATO, Akiyoshi Bio-nanotransporter Project, Kyoto University Katsura, Nishikyo-ku, Kyoto, Japan.
Shin-Ichi
S
Sawada
Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto, Japan. akiyoshi@bio.polym.kyoto-u.ac.jp.|JST-ERATO, Akiyoshi Bio-nanotransporter Project, Kyoto University Katsura, Nishikyo-ku, Kyoto, Japan. akiyoshi@bio.polym.kyoto-u.ac.jp.
Kazunari
K
Akiyoshi
D000818:Animals; D002417:Cattle; D004337:Drug Carriers / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D005936:Glucans / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000378:metabolism; D008280:Magnetics; D053768:Metal Nanoparticles / Q000737:chemistry*; D018613:Microscopy, Confocal; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism
D004337:Drug Carriers; D005290:Ferric Compounds; D005456:Fluorescent Dyes; D005936:Glucans; D007328:Insulin; D018832:Molecular Chaperones; D000080385:Nanogels; D011506:Proteins; C413692:polyethylene glycol polyethyleneimine nanogel; C000499:ferric oxide; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; C009109:pullulan; D011094:Polyethyleneimine
crosslinked nanogels; drug delivery; organic-inorganic nanomaterials; protein transduction; protein-based therapies