title: 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: Center for Pharmaceutical Biotechnology & Nanomedicine, Northeastern University, Boston, MA 02115, USA.
authors: Alexander
authors: A
authors: Koshkaryev
authors: Aleksandr
authors: A
authors: Piroyan
authors: Vladimir P
authors: VP
authors: Torchilin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001761:Bleomycin / Q000008:administration & dosage* / Q000737:chemistry; D048708:Cell Growth Processes / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage* / Q000737:chemistry; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000737:chemistry; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
chemical_list: D008081:Liposomes; D009842:Oligopeptides; D010714:Phosphatidylethanolamines; C448619:octaarginine; D001761:Bleomycin; C094877:dioleoyl phosphatidylethanolamine