title: Monoclonal antibody 2C5-modified doxorubicin-loaded liposomes with significantly enhanced therapeutic activity against intracranial human brain U-87 MG tumor xenografts in nude mice.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA.
authors.forename: Bhawna
authors.initials: B
authors.lastname: Gupta
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Torchilin
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D008081:Liposomes; D009707:Nucleosomes; D011092:Polyethylene Glycols; D004317:Doxorubicin