Polyoxometalate-Based Organic-Inorganic Hybrids as Antitumor Drugs

Small. 2015 Jun 24;11(24):2938-45. doi: 10.1002/smll.201500232. Epub 2015 Feb 26.

Abstract

Polyoxometalates (POMs) have shown encouraging antitumor activity. However, their cytotoxicity in normal cells and unspecific interactions with biomolecules are two major obstacles that impede the practical applications of POMs in clinical cancer treatment. Derivatization of POMs with more biocompatible organic ligands is expected to cause a synergetic effect and achieve improved bioactivity and biospecificity. Herein, the synthesis of an amphiphilic organic-inorganic hybrid is reported by grafting a long-chain organoalkoxysilane lipid onto a POM. The amphiphilic POM hybrid could spontaneously assemble into the vesicles and exhibits enhanced antitumor activity for human colorectal cancer cell lines (HT29) compared to that of parent POMs. This detailed study reveals that the amphiphilic nature of POM hybrids enables the as-formed vesicles to easily bind to the cell membranes and then be uptaken by the cells, thus leading to a substantial increase in antitumor activity. Such prominent antitumor action is mostly accomplished via cell apoptosis, which ultimately results in cell death. Our finding demonstrates that novel POM hybrids-based drugs with increased bioactivity could be obtained by decorating POMs with selective organic ligands.

Keywords: antitumor; composites; hybrid materials, biomaterials; organic-inorganic hybrid materials; polyoxometalates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A5 / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Dynamic Light Scattering
  • Endocytosis / drug effects
  • HT29 Cells
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Inorganic Chemicals / pharmacology*
  • Kinetics
  • Lipid Bilayers / chemistry
  • Organic Chemicals / pharmacology*
  • Propidium / metabolism
  • Surface Plasmon Resonance
  • Tungsten Compounds / pharmacology*

Substances

  • Annexin A5
  • Antineoplastic Agents
  • Inorganic Chemicals
  • Lipid Bilayers
  • Organic Chemicals
  • Tungsten Compounds
  • polyoxometalate I
  • Propidium