Functionalized nanoparticles crossing the brain-blood barrier to target glioma cells

Glioma is the most common tumor of the central nervous system (CNS), with a 5-year survival rate of <35%. Drug therapy, such as chemotherapeutic and immunotherapeutic agents, remains one of the main treatment modalities for glioma, including temozolomide, doxorubicin, bortezomib, cabazitaxel, dihydroartemisinin, immune checkpoint inhibitors, as well as other approaches such as siRNA, ferroptosis induction, etc. However, the filter function of the blood-brain barrier (BBB) reduces the amount of drugs needed to effectively target CNS tumors, making it one of the main reasons for poor drug efficacies in glioma. Thus, finding a suitable drug delivery platform that can cross the BBB, increase drug aggregation and retainment in tumoral areas and avoid accumulation in non-targeted areas remains an unsolved challenge in glioma drug therapy. An ideal drug delivery system for glioma therapy should have the following features: (1) prolonged drug life in circulation and effective penetration through the BBB; (2) adequate accumulation within the tumor (3) controlled-drug release modulation; (4) good clearance from the body without significant toxicity and immunogenicity, etc. In this regard, due to their unique structural features, nanocarriers can effectively span the BBB and target glioma cells through surface functionalization, providing a new and effective strategy for drug delivery. In this article, we discuss the characteristics and pathways of different nanocarriers for crossing the BBB and targeting glioma by listing different materials for drug delivery platforms, including lipid materials, polymers, nanocrystals, inorganic nanomaterials, etc.