Cellular and molecular targeted drug delivery in central nervous system cancers: advances in targeting strategies.

Central nervous system (CNS) cancers are among the most common and treatment-resistant diseases. The main reason for the low treatment efficiency of the disorders is the barriers against targeted delivery of anticancer agents to the site of interest, including the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). BBB is a strong biological barrier separating circulating blood from brain extracellular fluid that selectively and actively prevents cytotoxic agents and majority of anticancer drugs from entering the brain. BBB and BBTB are the major impediments against targeted drug delivery into CNS tumors. Nanotechnology and its allied modalities offer interesting and effective delivery strategies to transport drugs across BBB to reach brain tissue. Integrating anticancer drugs into different nanocarriers improves the delivery performance of the resultant compounds across BBB. Surface engineering of nanovehicles using specific ligands, antibodies and proteins enhances the BBB crossing efficacy as well as selective and specific targeting to the target cancerous tissues in CNS tumors. Multifunctional nanoparticles (NPs) have brought revolutionary advances in targeted drug delivery to brain tumors. This study reviews the main anatomical, physiological and biological features of BBB and BBTB in drug delivery and the recent advances in targeting strategies in NPs-based drug delivery for CNS tumors. Moreover, we discuss advances in using specific ligands, antibodies, and surface proteins for designing and engineering of nanocarriers for targeted delivery of anticancer drugs to CNS tumors. Finally, the current clinical applications and the perspectives in the targeted delivery of therapeutic molecules and genes to CNS tumors are discussed.