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.
Keywords: Targeted drug delivery, Brain tumors, Central nervous system, Blood-brain barrier, Blood-brain tumor barrier drug
delivery, Ligand targeting, Drug transport.
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