Applications of Gold Nanoparticles in Brain Diseases across the Blood-Brain Barrier

Brain diseases, including Alzheimer's disease (AD), brain tumors and Parkinson's disease (PD), pose heavy pressure on the public healthcare system. The main obstacle to vanquish brain diseases is the blood-brain barrier (BBB), which is a selective barrier mainly formed by brain endothelial cells. BBB prevents almost all drugs from reaching the brain, thereby hindering drug delivery. Over the past few decades, considerable signs of progress have been made in crossing the BBB and treating brain diseases. Gold nanoparticles (AuNPs) demonstrate the characteristics of adjustable size, unique optical properties, flexible surface modification, and good biocompatibility, which all contribute AuNPs as a promising candidate in biomedical fields. This article reviews the structure and properties of BBB, and discusses main transport routes through the BBB. Besides, nanoparticles, specially AuNPs applied in brain diseases as main drug delivery platforms, are systematically summarized, emphasizing several methods to modify AuNPs, including tuning particle size and surface modification, which are aimed at promoting BBB penetration or prolonging circulation time of AuNPs. In addition, AuNPs utilized in brain diseases are introduced in detail from the aspects of brain imaging, AD, brain tumors, and PD. Prospects and challenges that need to be considered in further investigations and clinical transformation of AuNPs used in brain diseases are also included, hoping to bring new insights into the applications of AuNPs in brain diseases.