Bleomycin in octaarginine-modified fusogenic liposomes results in improved tumor growth inhibition.

Abstract

Bleomycin (BLM) is an example of an anticancer drug that should be delivered into cytosol for its efficient therapeutic action. With this in mind, we developed octaarginine (R8)-modified fusogenic DOPE-liposomes (R8-DOPE-BLM). R8-modification dramatically increased (up to 50-fold) the cell-liposome interaction. R8-DOPE-liposomes were internalized via macropinocytosis and did not end up in the lysosomes. R8-DOPE-BLM led to a significantly stronger cell death and DNA damage in vitro relative to all controls. R8-DOPE-BLM demonstrated a prominent anticancer effect in the BALB/c mice bearing 4T1 tumors. Thus, R8-DOPE-BLM provided efficient intracellular delivery of BLM leading to strong tumor growth inhibition in vivo.

• Authors: Alexander Koshkaryev, Aleksandr Piroyan, Vladimir P Torchilin
• Journal: Cancer letters (Cancer Lett) Vol. 334 Issue 2 Pg. 293-301 (Jul 01 2013) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 22743614 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Liposomes
• Oligopeptides
• Phosphatidylethanolamines
• octaarginine
• Bleomycin
• dioleoyl phosphatidylethanolamine

Topics

• Animals
• Apoptosis (drug effects)
• Bleomycin (administration & dosage, chemistry)
• Cell Growth Processes (drug effects)
• Disease Models, Animal
• Female
• HeLa Cells
• Humans
• Liposomes (administration & dosage, chemistry)
• Mammary Neoplasms, Experimental (drug therapy, pathology)
• Mice
• Mice, Inbred BALB C
• Microscopy, Confocal
• Oligopeptides (administration & dosage, chemistry)
• Phosphatidylethanolamines (administration & dosage, chemistry)
• Random Allocation
• Xenograft Model Antitumor Assays