Monoclonal antibody 2C5-modified doxorubicin-loaded liposomes with significantly enhanced therapeutic activity against intracranial human brain U-87 MG tumor xenografts in nude mice.
Liposomes, modified with monoclonal antibodies, are suitable carriers for targeted delivery of chemotherapeutic drugs into brain tumors. Here, we investigate the therapeutic efficacy of monoclonal anticancer antibody 2C5-modified long-circulating liposomes (LCL) loaded with doxorubicin (2C5-DoxLCL) for the treatment of U-87 MG human brain tumors in an intracranial model in nude mice. In vitro, 2C5-DoxLCL is significantly more effective in killing the U-87 MG tumor cells than Doxil (commercial doxorubicin-loaded PEGylated LCL) or DoxLCL modified with a non-specific IgG. 2C5-immunoliposomes also demonstrate a significantly higher accumulation in U-87 MG tumors compared to all controls in a subcutaneous model. The treatment of intracranial U-87 MG brain tumors in nude mice with 2C5-DoxLCL provides a significant therapeutic benefit over control formulations, substantially reducing the tumor size and almost doubling the survival time. Thus, monoclonal antibody 2C5-modified LCL can specifically target the anticancer drugs to brain tumors, leading to improved therapeutic treatment of brain tumor in an intracranial model, in vivo.
Gupta
Bhawna
B
Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA.
Torchilin
Vladimir P
VP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis; D001254:Astrocytoma / Q000188:drug therapy* / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002540:Cerebral Cortex; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D007267:Injections; D007279:Injections, Subcutaneous; D008081:Liposomes / Q000008:administration & dosage; D051379:Mice; D008819:Mice, Nude; D009707:Nucleosomes / Q000276:immunology; D011092:Polyethylene Glycols / Q000008:administration & dosage; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D008081:Liposomes; D009707:Nucleosomes; D011092:Polyethylene Glycols; D004317:Doxorubicin