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Magnetically Navigated Protein Transduction In Vivo using Iron Oxide‐Nanogel Chaperone Hybrid
Author(s) -
Kawasaki Riku,
Sasaki Yoshihiro,
Nishimura Tomoki,
Katagiri Kiyofumi,
Morita Keiichi,
Sekine Yurina,
Sawada Shinichi,
Mukai Sadaatsu,
Akiyoshi Kazunari
Publication year - 2021
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.202001988
Subject(s) - in vivo , nanogel , saporin , transduction (biophysics) , signal transduction , microbiology and biotechnology , cancer cell , chemistry , biology , cancer research , biophysics , in vitro , biochemistry , materials science , drug delivery , cancer , nanotechnology , cytotoxicity , immunotoxin , genetics
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.