Drug delivery and targeting to brain tumors: considerations for crossing the blood-brain barrier

Introduction: The blood-brain barrier (BBB) selectively impedes the transportation of drug molecules into the brain, which makes the drug delivery and targeting of brain tumors very challenging. Areas covered: Having surveyed the recent literature, comprehensive insights are given into the impacts of the BBB on the advanced drug delivery and targeting modalities for brain tumors. Expert opinion: Brain capillary endothelial cells form the BBB in association with astrocytes, pericytes, neurons, and extracellular matrix. Coop of these forms the complex setting of neurovascular unite. The BBB maintains the brain homeostasis by restrictive controlling of the blood circulating nutrients/substances trafficking. Despite substantial progress on therapy of brain tumors, there is no impeccable strategy to safely deliver chemotherapeutics into the brain. Various strategies have been applied to deliver chemotherapeutics into the brain (e.g. BBB opening, direct delivery by infusion, injection, microdialysis, and implants, and smart nanosystems), which hold different pros and cons. Of note, smart nanoscale multifunctional nanomedicines can serve as targeting, imaging, and treatment modality for brain tumors. Given that aggressive brain tumors (e.g. gliomas) are often unresponsive to any treatments, an in-depth understanding of the molecular/cellular complexity of brain tumors might help the development of smart and effective treatment modalities.