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ACS Nanoに論文が受理されました。（細胞内レドックス応答型アルブミンナノ粒子の創製と肝炎治療への応用）

2023/09/01

ACS Nanoに論文が受理されました。（細胞内レドックス応答型アルブミンナノ粒子の創製と肝炎治療への応用）

Encapsulation of an Antioxidant in Redox-Sensitive Self-Assembled Albumin Nanoparticles for the Treatment of Hepatitis

Kengo Yasuda 1, Hitoshi Maeda 1, Ryo Kinoshita 1, Yuki Minayoshi 1, Yuki Mizuta 1, Yuka Nakamura 1, Shuhei Imoto 2 3, Koji Nishi 2, Keishi Yamasaki 2, Mina Sakuragi 4, Teruya Nakamura 1, Mayumi Ikeda-Imafuku 5, Yasunori Iwao 5, Yu Ishima 6, Tatsuhiro Ishida 6, Yasuko Iwakiri 7, Masaki Otagiri 2, Hiroshi Watanabe 1, Toru Maruyama 1
・PMID: 37579503
・DOI: 10.1021/acsnano.3c02877

Abstract:

Hepatitis is an inflammation of the liver caused by the inadequate elimination of reactive oxygen species (ROS) derived from Kupffer cells. Edaravone is clinically used as an antioxidant but shows poor liver distribution. Herein, we report on the design of a Kupffer cell-oriented nanoantioxidant based on a disulfide cross-linked albumin nanoparticle containing encapsulated edaravone (EeNA) as a therapeutic for the treatment of hepatitis. Since the edaravone is bound to albumin, this results in a soluble and stable form of edaravone in water. Exchanging the intramolecular disulfide bonds to intermolecular disulfide bridges of albumin molecules allowed the preparation of a redox responsive albumin nanoparticle that is stable in the blood circulation but can release drugs into cells. Consequently, EeNA was fabricated by the nanoscale self-assembly of edaravone and albumin nanoparticles without the additives that are contained in commercially available edaravone preparations. EeNA retained its nanostructure under serum conditions, but the encapsulated edaravone was released efficiently under intracellular reducing conditions in macrophages. The EeNA was largely distributed in the liver and subsequently internalized into Kupffer cells within 60 min after injection in a concanavalin-A-induced hepatitis mouse. The survival rate of the hepatitis mice was significantly improved by EeNA due to the suppression of liver necrosis and oxidative stress by scavenging excessive ROS. Moreover, even through the postadministration, EeNA showed an excellent hepatoprotective action as well. In conclusion, EeNA has the potential for use as a nanotherapeutic against various types of hepatitis because of its Kupffer cell targeting ability and redox characteristics.

Keywords: albumin; edaravone; hepatitis; nanoparticle; oxidative stress; targeted delivery.