Magnetically Navigated Protein Transduction In Vivo using Iron Oxide‐Nanogel Chaperone Hybrid
| Autor: | Sada-atsu Mukai, Kazunari Akiyoshi, Yoshihiro Sasaki, Yurina Sekine, Shin-ichi Sawada, Kei-ichi Morita, Riku Kawasaki, Tomoki Nishimura, Kiyofumi Katagiri |
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| Rok vydání: | 2021 |
| Předmět: |
Saporin
Biomedical Engineering Nanogels Pharmaceutical Science 02 engineering and technology 010402 general chemistry Ferric Compounds 01 natural sciences Biomaterials Magnetics chemistry.chemical_compound Transduction (genetics) In vivo biology Cell growth 021001 nanoscience & nanotechnology 0104 chemical sciences Cell biology chemistry Chaperone (protein) biology.protein 0210 nano-technology Iron oxide nanoparticles Intracellular Molecular Chaperones Nanogel |
| Zdroj: | Advanced Healthcare Materials. 10:2001988 |
| ISSN: | 2192-2659 2192-2640 |
| DOI: | 10.1002/adhm.202001988 |
| Popis: | Systems for "protein transduction," intracellular delivery of functional proteins, are needed to address deliverability challenges of protein therapeutics. However, in vivo protein transduction remains challenging because of instability in serum, extracellular protease digestion and rapid excretion from the bloodstream. Here, a magnetically guided in vivo protein transduction using magnetic nanogel chaperone (MC) composed of iron oxide nanoparticles and a polysaccharide nanogel, a protein carrier inspired by "catch and release" mechanisms of molecular chaperones is demonstrated. The MC system enables efficient delivery of anti-cancer proteins, saporin and RNaseA, into cultured tumor lines and inhibits cell proliferation, mainly via apoptosis. Magnetic in vivo protein transduction via intravenous whole body administration is demonstrated in a fibrosarcoma model. By in vivo optical imaging, MC accumulated in tumor tissues under magnetic field three times more than without irradiation. With subcutaneous injection, saporin is delivered by MC to the cytoplasm in magnetically targeted tissues. In an oral cancer model, MC-delivered magnetically targeted saporin decreased tumor volume without significant body weight changes and no regrowth of tumor at 3 months after complete regression. Protein transduction with MC shows promise for cancer therapeutics and, potentially, for regenerative medicine and other biomedical applications. |
| Databáze: | OpenAIRE |
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