Tailored doxorubicin-hyaluronan conjugate as a potent anticancer glyco-drug: an alternative to prodrug approach

Macromol Biosci. 2014 Mar;14(3):327-33. doi: 10.1002/mabi.201300383. Epub 2013 Oct 15.

Abstract

Releasibility of doxorubicin from drug-conjugates is believed to be a prerequisite for its anti-cancer activity. Here, a new glyco-drug approach that circumvents the releasibility restriction is reported, opening a new possibility to design efficient, target specific drug delivery system. It is discovered that stable amide coupling of doxorubicin (DOX) tohyaluronan (HA) shows dose dependent cytotoxicity to CD44 positive human coloncancer cells (HCT116) as compared to human breast cancer cells(MCF-7) and mouse fibroblast cells (NIH-3T3), which express less CD44 receptor. This direct conjugation approach is an easy scalable strategy that could be adopted to design innocuous anti-tumor nanoparticle formulations.

Keywords: anticancer therapy; drug delivery; endocytosis; glyco-drug; hyaluronic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / chemistry
  • Antibiotics, Antineoplastic / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology*
  • Drug Carriers
  • Gene Expression
  • Glycoconjugates / chemistry
  • Glycoconjugates / pharmacology*
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / metabolism
  • Hyaluronic Acid / chemistry*
  • Mice
  • NIH 3T3 Cells
  • Organ Specificity
  • Prodrugs
  • Protein Binding

Substances

  • Antibiotics, Antineoplastic
  • Drug Carriers
  • Glycoconjugates
  • Hyaluronan Receptors
  • Prodrugs
  • Doxorubicin
  • Hyaluronic Acid