α1-Acid Glycoprotein Has the Potential to Serve as a Biomimetic Drug Delivery Carrier for Anticancer Agents

Kotaro Matsusaka, Yu Ishima, Hitoshi Maeda, Ryo Kinoshita, S. Ichimizu, Kazuaki Taguchi, Victor Tuan Giam Chuang, Koji Nishi, Keishi Yamasaki, Masaki Otagiri, Hiroshi Watanabe, Toru Maruyama

Research output: Contribution to journalArticle

Abstract

Nanosize plasma proteins could be used as a biomimetic drug delivery system (DDS) for cancer treatment when loaded with anticancer drugs based on the fact that plasma proteins can serve as a source of nutrients for cancer cells. This prompted us to investigate the potential of α1-acid glycoprotein (AGP) for this role because it is a nanosize plasma protein and binds a variety of anticancer agents. Pharmacokinetic analyses indicated that AGP is distributed more extensively in tumor tissue than human serum albumin, which was already established as a cancer DDS carrier. AGP is possibly being incorporated into tumor cells via endocytosis pathways. Moreover, a synthetic AGP-derived peptide which possesses a high ability to form an α-helix, as deduced from the primary structure of AGP, was also taken up by the tumor cells. AGP loaded with anticancer agents, such as paclitaxel or nitric oxide, efficiently induced tumor cell death. These results suggest that AGP has the potential to be a novel DDS carrier for anticancer agents.

Original languageEnglish
JournalJournal of Pharmaceutical Sciences
DOIs
Publication statusAccepted/In press - 2019 Jan 1

Keywords

  • anticancer agents
  • cancer
  • DDS carrier
  • orosomucoid
  • α-acid glycoprotein

ASJC Scopus subject areas

  • Pharmaceutical Science

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    Matsusaka, K., Ishima, Y., Maeda, H., Kinoshita, R., Ichimizu, S., Taguchi, K., Giam Chuang, V. T., Nishi, K., Yamasaki, K., Otagiri, M., Watanabe, H., & Maruyama, T. (Accepted/In press). α1-Acid Glycoprotein Has the Potential to Serve as a Biomimetic Drug Delivery Carrier for Anticancer Agents. Journal of Pharmaceutical Sciences. https://doi.org/10.1016/j.xphs.2019.07.002