Marshall Cress, Angela Spurgeon, Mark F McLaughlin, Tiffany Remsen, Douglas C Miller, J David Robertson and Paul H Pevsner
Crossing the Blood-Brain Barrier with Antibody-Labeled, Gold-Coated Nanoconjugates: A Preliminary Step in Targeting and Eradicating Brain Tumors
This paper shows ultrastructural proof of principle that antibodylabeled nanoconjugates can cross the blood-brain barrier and bind to their targeted antigens. Gold-coated nanoconjugates labeled with monoclonal antibodies targeting brain antigens-specifically, the synaptophysin and glial fibrillary acidic proteins-were injected intravascularly into 45 Balb/c mice. Through electron microscopy a portion of the nanoconjugates were shown to have crossed the blood-brain barrier and become localized either on the intermediate filaments in the astrocytic cytoplasm (anti-glial fibrillary acidic proteins) or presynaptic membranes (anti-synaptophysin). Three of the authors have already reported on a similar and successful use of radioactive nanoconjugates to target antigens in a syngeneic murine lung tumor model using CMT-6 breast cancer cells. This proof of principle supported by concrete evidence does not include an analysis of the mechanism by which the nanoconjugates crossed the blood-brain barrier. The success of targeting proteins in the brain and, by implication, antigens in brain tumors, has immense potential for the treatment of a wide variety of metastases and tumors, including brain cancers such as glioblastoma.
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