As an essential component of immunotherapy, monoclonal antibodies (mAbs) have emerged as a class of powerful therapeutics for treatment of a broad range of diseases. For central nervous system (CNS) diseases, however, the efficacy remains limited due to their inability to enter the CNS. A platform technology is reported here that enables effective delivery of mAbs to the CNS for brain tumor therapy. This is achieved by encapsulating the mAbs within nanocapsules that contain choline and acetylcholine analogues; such analogues facilitate the penetration of the nanocapsules through the brain–blood barrier and the delivery of mAbs to tumor sites. This platform technology uncages the therapeutic power of mAbs for various CNS diseases that remain poorly treated. A bioinspired platform technology is developed, which enables effective delivery of monoclonal antibodies to the central nervous system for brain tumor therapy via intravenous administration. This platform technology uncages the therapeutic power of mAbs for various CNS diseases that remain poorly treated.