Albumin-Based Nitric Oxide Traffic System for the Treatment of Intractable Cancers

• Ishima Yu

  Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, 
Tokushima University Graduate School

Abstract

Biomacromolecules (>40 kDa) have been developed as drug delivery system (DDS) carriers of low-molecular weight drugs to promote these drugs’ uptake by cancer tissues via enhanced permeability and retention (EPR) effects. Human serum albumin (HSA) has been found to accumulate in cancer tissues via this EPR effect. HSA is the most abundant protein in serum, which performs essential physiological functions such as the transportation of many endogenous and exogenous ligands. Nitric oxide (NO) is a very small ligand of HSA; it is a unique and diffusible molecular messenger that plays a central role in mammalian physiology. Although the in vivo half-life of NO is extremely short, HSA could prolong the half-life of NO via S-nitrosation at the position of Cys-34. S-Nitrosated HSA (mono-SNO-HSA) is called an ‘Endogenous NO traffic protein,’ due to the highly stable S-nitroso form in circulating blood, and to the efficiency of S-transnitrosation in cells that require NO. Mono-SNO-HSA possesses a very strong cytoprotective action via the induction of heme oxygenase-1. On the other hand, HSA reinforced with approximately seven NO molecules (poly-SNO-HSA), which we developed by means of chemical modification, possesses multiple anticancer activities. Our previous data clarified that the high expression of protein disulfide isomerase on the surface of cancer cells plays a very important role in the anticancer action of poly-SNO-HSA. In this review, we focus on the advantage of poly-SNO-HSA in treating intractable cancers from the viewpoint of drug delivery systems and drug resistance.

Journal

• Biological and Pharmaceutical Bulletin

  Biological and Pharmaceutical Bulletin 40 (2), 128-134, 2017

  The Pharmaceutical Society of Japan

Keywords

• human serum albumin
• nitric oxide
• <i>S</i>-nitrosation
• drug delivery system
• anticancer activity
• enhanced permeability and retention effect

Details

• CRID: 1390001204634543872
• NII Article ID: 130005308413
• NII Book ID: AA10885497
• DOI: 10.1248/bpb.b16-00867
• ISSN: 13475215
• ISSN: 09186158
• NDL BIB ID: 027871506
• PubMed: 28154250
• Web Site: http://id.ndl.go.jp/bib/027871506
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I027871506
• Web Site: https://www.jstage.jst.go.jp/article/bpb/40/2/40_b16-00867/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2017307733
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed