Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2116304 | Cancer Letters | 2013 | 9 Pages |
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.