EGF-liposomes promote efficient EGFR targeting in xenograft colocarcinoma model

Nanomedicine (Lond). 2016;11(5):465-77. doi: 10.2217/nnm.15.208. Epub 2016 Feb 19.

Abstract

Aim: Development of EGF-liposomes (LP-EGF) for selective molecules delivery in tumors expressing EGFR.

Material & methods: In vitro cellular interaction of EGF-LP and nontargeted liposomes (LP-N) was assayed at 37 and 4 °C in cells expressing different EGFR levels. Receptor-mediated uptake was investigated by competition with a monoclonal antibody anti-EGFR. Selective intracellular drug delivery and efficacy was tested by oxaliplatin encapsulation. In vivo biodistribution of LP-N and LP-EGF was done in xenograft model.

Results: LP-EGF was internalized by an active and selective mechanism through EGFR without receptor activation. Oxaliplatin LP-EGF decreased IC50 between 48 and 13% in cell EGFR+. LP-EGF was accumulated in tumor over 72 h postdosing, while LP-N in spleen.

Conclusion: LP-EGF represents an attractive nanosystem for cancer therapy or diagnosis.

Keywords: EGF; EGFR; cetuximab; colorectal cancer; oxaliplatin; targeted liposomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology
  • Drug Delivery Systems*
  • Epidermal Growth Factor / administration & dosage
  • Epidermal Growth Factor / chemistry
  • Epidermal Growth Factor / genetics*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • Humans
  • Liposomes / administration & dosage
  • Liposomes / chemistry
  • Mice
  • Molecular Targeted Therapy
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / chemistry
  • Oxaliplatin
  • Xenograft Model Antitumor Assays

Substances

  • Liposomes
  • Organoplatinum Compounds
  • Oxaliplatin
  • Epidermal Growth Factor
  • EGFR protein, human
  • ErbB Receptors