Utilization of a right-handed coiled-coil protein from archaebacterium Staphylothermus marinus as a carrier for cisplatin

Anticancer Res. 2009 Jan;29(1):11-8.

Abstract

Background: The nano-sized right-handed coiled-coil (RHCC) protein, originating from the archaebacterium Staphylothermus marinus, is stable at high salt concentrations, high temperatures, high pressures and extremes of pH. Its crystal structure reveals four hydrophobic cavities which can incorporate heavy metals. Nano-sized compounds have been used to carry cytotoxic drugs to tumours, avoiding delivery to healthy tissue, in part due to enhanced permeability in tumour blood vessels (enhanced permeability and retention effect).

Materials and methods: The ability of RHCC to carry the platinum-containing chemotherapeutic drug cisplatin to cells, while retaining the cytotoxic potential was tested both in vitro and in vivo.

Results: RHCC was able to bind and enter cells in vitro and was not severely toxic or immunogenic in mice. Moreover, RHCC incorporated cisplatin, without inhibiting the cytotoxic potential of the drug against tumour cell lines in vitro or in vivo.

Conclusion: RHCC can be used as a carrier of cisplatin without abrogating the effect of the drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, CD / immunology
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Archaeal Proteins / administration & dosage*
  • Archaeal Proteins / chemistry
  • Archaeal Proteins / pharmacokinetics
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Line, Tumor
  • Cisplatin / administration & dosage*
  • Cisplatin / chemistry
  • Cisplatin / pharmacokinetics
  • Desulfurococcaceae
  • Drug Carriers
  • Flow Cytometry
  • Humans
  • Interferon-gamma / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, SCID
  • Models, Molecular
  • Protein Structure, Secondary
  • Xenograft Model Antitumor Assays

Substances

  • Antigens, CD
  • Antineoplastic Agents
  • Archaeal Proteins
  • Drug Carriers
  • Interferon-gamma
  • Cisplatin