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

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.

► Octaarginine (R8)-modified fusogenic DOPE-liposomes were developed for improved cytosolic delivery of bleomycin (BLM).
► R8-modification dramatically increased (up to 50-fold) the cell-liposome interaction.
► R8-DOPE-liposomes were internalized via macropinocytosis and released their hydrophilic loads to the cytoplasm.
► BLM-loaded R8-DOPE-liposomes demonstrated a strong cytotoxic effect and DNA damage in vitro.
► Treatment of 4T1 xenograft-bearing mice with R8-DOPE-BLM strongly inhibited the tumor growth.