Inorganic nano-drug delivery systems for crossing the blood–brain barrier: Advances and challenges

The blood–brain barrier (BBB) exists between plasma and brain tissue. It comprises a capillary wall and glial cells and prevents external substances, including therapeutic agents, from entering the brain. The prevention has caused difficulty in treating central nervous system (CNS)-associated diseases. With the development of nanotechnology and a more in-depth understanding of the BBB, various nano-drug delivery systems (NDDS) have been developed and used as promising BBB-crossing agents to achieve efficient delivery and release of drugs to the CNS. Herein, we summarize the recent progress in developing inorganic NDDS for crossing the BBB, including metal-based nanoparticles (NPs), Si NPs, Se NPs, semiconductor quantum dots, and carbon nanostructures. The mechanisms of these inorganic NDDS on crossing BBB have been reviewed. Moreover, the influence factors, including the morphology, size, surface charge, and chemical groups that affect the BBB crossing efficacy of these inorganic NDDS, are discussed. The advantages and challenges of these NDDS may face in future clinical use are presented. This review provides the overall understanding of inorganic NDDS for crossing the BBB, offering new paths that may be used for treating CNS diseases.