ABSTRACT
The selectivity of PEGylated immunoliposomes based on monoclonal antibodies against GFAP and the E2 extracellular loop of connexin 43 (MAbE2Cx43) with respect to the focus of a glioma was estimated in experiments on animals with intracranial C6 glioma. Stealth immunoliposomes were labeled with 2 alternative labels, a fluorescent (Dil C18) and a paramagnetic (Gd-DTPA) one. Fluorescent-labeled liposomal nanocontainers were detected at the periphery of the glioma, where the target antigens were overexpressed, 48 hours after injection. Dynamic T1 MRI of rats injected with paramagnetic immunoliposomes carrying MAbE2Cx43 showed distinct accumulation of the paramagnetic contrast agent at the periphery of the glioma, which began 6 hours after administration. These data suggest that immunoliposomal nanocontainers based on antibodies against GFAP and the E2 extracellular fragment of connexin 43 are suitable for targeted delivery of diagnostic and therapeutic drugs to the peritumoral invasion zone of high-grade gliomas. FROM THE CLINICAL EDITOR: PEGylated immunoliposomes based on monoclonal antibodies against GFAP and the E2 extracellular loop of connexin 43 were investigated in animals with intracranial C6 glioma. These immunoliposomal nanocontainers were found suitable for targeted delivery of diagnostic and therapeutic drugs to the peritumoral invasion zone of high-grade gliomas.
Subject(s)
Brain Neoplasms/pathology , Glioma/pathology , Liposomes/chemical synthesis , Liposomes/immunology , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/immunology , Brain Neoplasms/immunology , Connexin 43/immunology , Drug Carriers/chemical synthesis , Female , Gadolinium DTPA/chemistry , Glial Fibrillary Acidic Protein/immunology , Glioma/immunology , Liposomes/administration & dosage , Magnetic Resonance Imaging , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Neoplasms, Experimental/chemistry , Neoplasms, Experimental/immunology , Polyethylene Glycols/chemistry , RatsABSTRACT
The selectivity of monoclonal antibodies against the E2 extracellular fragment of connexin 43 (Cx43) for a glioma focus was studied in in vivo experiments on animals with intracranial C6 glioma. Antibodies labeled with two alternative labels, the radioisotope (125)I and the fluorophore Alexa 660, were intravenously injected to rats with 18-day gliomas. Seventy-two hours after injection, (125)I-labeled antibodies accumulated in the hemisphere where the glioma was located to a concentration of 0.27 ± 0.01% of the injected dose per gram of wet weight, which exceeded their accumulation in the liver, spleen, and other organs. Fluorescent-labeled antibodies against the Cx43 fragment E2 specifically visualized cells in the peritumoral astroglial bank (a zone of active invasion of glioma cells). Double immunofluorescent visualization using antibodies against the Cx43 fragment E2 and glial fibrillar acidic protein (GFAP) showed that only a small proportion of the cells that bound the antibodies injected into the blood circulation were reactive astrocytes, whereas most of these cells were GFAP-negative and morphologically corresponded to astroblasts. These results suggest that antibodies against the extracellular Cx43 fragment E2 can be used for targeted transport of diagnostic and therapeutic drugs to the peritumoral invasion zone of high-grade gliomas.
