Targeted delivery of liposomal nanocontainers to the peritumoral zone of glioma by means of monoclonal antibodies against GFAP and the extracellular loop of Cx43

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 EditorPEGylated 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.

Graphical AbstractTargeted nanocontainers were designed on the base of PEGylated liposomes labeled with Dil or Gd–DTPA and monoclonal antibodies against GFAP or the E2 extracellular loop of connexin 43. These two target proteins are overexpressed in the peritumoral zone of high-grade gliomas, where the invasion process is the most intense.The immunoliposomal nanocontainers were detected at the periphery of the glioma using both fluorescent microscopy and dynamic MRI. Thus the nanocontainers based on antibodies against GFAP and Cx43 are suitable for targeted delivery of diagnostic and therapeutic drugs to the peritumoral invasion zone of high-grade gliomas.Figure optionsDownload high-quality image (296 K)Download as PowerPoint slide