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Cytosolic protein delivery using ultrasound-guided vaporization of perfluorocarbon nano-droplets
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  • Satoshi Yamaguchi,
  • Miho Kisaka,
  • Kotaro Higashi,
  • Ayumu Ishijima,
  • Takashi Azuma,
  • Keiichi Nakagawa,
  • Yoshikazu Shibasaki,
  • Ichiro Sakuma,
  • Akimitsu Okamoto
Satoshi Yamaguchi
The University of Tokyo

Corresponding Author:yamaguchi@bioorg.rcast.u-tokyo.ac.jp

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Miho Kisaka
The University of Tokyo
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Kotaro Higashi
The University of Tokyo
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Ayumu Ishijima
The University of Tokyo
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Takashi Azuma
The University of Tokyo
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Keiichi Nakagawa
The University of Tokyo
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Yoshikazu Shibasaki
The University of Tokyo
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Ichiro Sakuma
The University of Tokyo
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Akimitsu Okamoto
The University of Tokyo
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Abstract

Ultrasound-guided protein delivery is promising for site-specific control of cellular functions in the deep interior of the body in a noninvasive manner. Herein, we propose a method for cytosolic protein delivery based on ultrasound-guided intracellular vaporization of perfluorocarbon nano-droplets. The nano-droplets were conjugated with cargo proteins through a bio-reductively cleavable linker and introduced into living cells via antibody-mediated binding to a cell-surface receptor, which gets internalized through endocytosis. After the cells were exposed to ultrasound for endosomal escape of proteins, the ultrasound-responsive cytosolic release of a cargo enzyme was confirmed by visualizing the hydrolysis of the fluorogenic substrate using confocal microscopy. Moreover, a significant decrease in cell viability was achieved via the release of a cytotoxic protein in response to ultrasound treatment. The results of this study provide the proof of a principle that protein-conjugated nano-droplets can be used as carriers in ultrasound-guided cytosolic delivery of proteins.
10 Jan 2023Submitted to Biotechnology Journal
10 Jan 2023Submission Checks Completed
10 Jan 2023Assigned to Editor
17 Jan 2023Reviewer(s) Assigned
04 Mar 2023Review(s) Completed, Editorial Evaluation Pending
10 Mar 2023Editorial Decision: Revise Minor
23 Mar 20231st Revision Received
24 Mar 2023Submission Checks Completed
24 Mar 2023Assigned to Editor
24 Mar 2023Reviewer(s) Assigned
17 Apr 2023Review(s) Completed, Editorial Evaluation Pending
19 Apr 2023Editorial Decision: Accept