Dual delivery of carbon monoxide and doxorubicin using haemoglobin-albumin cluster: proof of concept for well-tolerated cancer therapy

Chihiro Ito, Kazuaki Taguchi, Taiga Yamada, Kengo Hanaya, Yuki Enoki, Takeshi Sugai, Teruyuki Komatsu, Kazuaki Matsumoto

研究成果: Article査読

抄録

A serious concern of doxorubicin (DOX) therapy is that it causes severe adverse effects, particularly cardiotoxicity. Carbon monoxide (CO) possesses powerful cytoprotective effects against drug-induced organ injury and is expected to ameliorate DOX-induced cardiotoxicity. In this study, a dual carrier of DOX and CO (CO-HemoAct-DOX) was fabricated based on a haemoglobin-albumin cluster (HemoAct), which is a protein cluster with a haemoglobin core structure wrapped by serum albumin. CO-HemoAct-DOX was synthesised by binding CO to a haemoglobin core and covalently conjugating (6-maleimidocaproyl)hydrazone derivative of DOX to an albumin shell. The average DOX/cluster ratio was about 2.6. In the in vitro cytotoxicity assay against cancer cells, the anti-tumour activity of CO-HemoAct-DOX was 10-fold lower than that of DOX in a 2D-cultured model, whereas CO-HemoAct-DOX suppressed the growth of tumour spheroids to the same extent as DOX in the 3D-cultured model. In colon-26 tumour-bearing mice, CO-HemoAct-DOX achieved DOX delivery to the tumour site and alleviated tumour growth more effectively than DOX. Furthermore, CO-HemoAct attenuated DOX-induced cardiomyocyte atrophy in H9c2 cells and elevated the levels of cardiac biomarkers in mice exposed to DOX. These results suggest that the dual delivery of CO and DOX using HemoAct is a promising strategy as an anti-tumour agent to realise well-tolerated cancer therapy with minimal cardiotoxicity.

本文言語English
ページ(範囲)5600-5608
ページ数9
ジャーナルJournal of Materials Chemistry B
12
23
DOI
出版ステータスPublished - 2024 5月 7

ASJC Scopus subject areas

  • 化学一般
  • 生体医工学
  • 材料科学一般

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