Versatile nanomaterials for Alzheimer's disease: Pathogenesis inspired disease-modifying therapy

• Published in: Journal of controlled release 2022-05, Vol.345, p.38-61
• Main Authors: Xi, Yilong, Chen, Yun, Jin, Yi, Han, Guochen, Song, Mingjie, Song, Tingting, Shi, Yang, Tao, Ling, Huang, Zewei, Zhou, Jianping, Ding, Yang, Zhang, Huaqing
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - pathology; Alzheimer's disease; BBB; Biological Transport; Blood-Brain Barrier - pathology; Combination therapy; Disease-modifying therapeutics; Humans; Nanomaterials; Nanomedicine; Nanostructures - therapeutic use; Pathogenesis inspired design
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2022.02.034

Current therapeutic strategies for Alzheimer's disease (AD) face the dilemma of no effective drugs that can delay the onset or slow the disease progression. Despite tremendous effort being involved, several anti-AD drugs come into clinical trials but with a moderate-to-poor success rate due to the complex AD pathogenesis and the blood-brain barrier (BBB). Insight into the complex AD pathogenesis is enabling new inspiration that have the potential to help improve our understanding and design of anti-AD nanomedicine. Herein, the complex AD pathogenesis and interaction between different therapeutic targets are summarized and highlighted, and key challenges facing translation of anti-AD nanomedicine from benchtop to bedside are discussed. Following combing through the complex pathogenesis and a contextual overview of clinical status of anti-AD compounds, we discuss the recent advances of exploring versatile nanomaterials in AD treatment from the pathogenesis. The focus here is especially on how to design pathogenesis-inspired nanomaterials for delivering therapeutics cross BBB and modulating the AD pathology by themselves as active ingredients. Collectively, this review highlights the pathogenesis-oriented nanomedicine design and provides with an easily accessible guide to the key opportunities and challenges currently facing the anti-AD nanomedicine. Alzheimer's disease (AD) is characterized with complex pathogenesis, including abnormal amyloid deposits, tauopathy, neuroinflammation and so on, and the versatile nanomaterials has been applied to modulate the pathogenic targets for efficient inhibition or reversal of AD progression. Herein, we have reviewed the latest advances of the pathogenesis inspired design of nanomaterials for AD disease-modifying therapies and discussed the bottleneck of current AD therapies, thus providing an optimized design principles for the further anti-AD drug development. [Display omitted]