Development of X-ray contrast agents using single nanometer-sized gold nanoparticles and lactoferrin complex and their application in vascular imaging

Tomoya Inose, Narufumi Kitamura, Mayumi Takano, Masayuki Tokunaga, Norikazu Une, Chihiro Kato, Mayu Tayama, Yukina Kobayashi, Noriko Yamauchi, Daisuke Nagao, Takuji Aimiya, Naoko Furusawa, Yasushi Nakano, Yoshio Kobayashi, Kohsuke Gonda

Research output: Contribution to journalArticlepeer-review

Abstract

The technology to accurately image the morphology of tumor vessels with X-ray contrast agents is important to clarify mechanisms underlying tumor progression and evaluate the efficacy of chemotherapy. However, in clinical practice, iodine-based contrast agents present problems such as short blood retention owing to a high clearance ability and insufficient X-ray absorption capacity when compared with other high atomic number elements. To resolve these issues, gold nanoparticles (AuNPs), with a high atomic number, have attracted a great deal of attention as contrast agents for angiography, and have been employed in small animal models. Herein, we developed novel contrast agents using AuNPs and captured changes in tumor vessel morphology with time using X-ray computed tomography (CT). First, glutathione-supported single nanometer-sized AuNPs (sAu/GSH) (diameter, 2.2 nm) were fabricated using tetrakis(hydroxymethyl)phosphonium chloride as a reducing agent. The sAu/GSH particles were intravenously injected into mice, remained in vessels for a few minutes, and were then excreted by the kidneys after 24 h, similar to the commercial contrast agent iopamidol. Next, the Au/GSH and lactoferrin (sAu/GSH-LF) (long axis size, 17.3 nm) complex was produced by adding lactoferrin to the sAu/GSH solution under the influence of a condensing agent. On intravenously administering sAu/GSH-LF to mice, the blood retention time was 1−3 h, which was considerably longer than that observed with iopamidol and sAu/GSH. Moreover, we succeeded in imaging morphological changes in identical tumor vessels for several days using X-ray CT with sAu/GSH-LF.

Original languageEnglish
Article number111732
JournalColloids and Surfaces B: Biointerfaces
Volume203
DOIs
Publication statusPublished - 2021 Jul

Keywords

  • Angiography
  • Contrast agent
  • Gold nanoparticle
  • Lactoferrin
  • Tumor vessel
  • X-ray CT imaging

ASJC Scopus subject areas

  • Biotechnology
  • Surfaces and Interfaces
  • Physical and Theoretical Chemistry
  • Colloid and Surface Chemistry

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