Glucose-modified BSA/procyanidin C1 NPs penetrate the blood-brain barrier and alleviate neuroinflammation in Alzheimer's disease models

• Published in: International journal of biological macromolecules Vol. 268; no. Pt 1; p. 131739
• Main Authors: Duan, Linyan, Hao, Zhizhong, Ji, Rong, Li, Xingfan, Wang, Hao, Su, Yujing, Guan, Fangxia, Ma, Shanshan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2024
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer's disease; Animals; Biflavonoids - chemistry; Biflavonoids - pharmacology; Blood-brain barrier; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Catechin - analogs & derivatives; Catechin - chemistry; Catechin - pharmacology; Disease Models, Animal; Glucose - metabolism; Humans; Male; Mice; Nanoparticles; Nanoparticles - chemistry; Neuroinflammation; Neuroinflammatory Diseases - drug therapy; Neuroinflammatory Diseases - metabolism; Proanthocyanidins - chemistry; Proanthocyanidins - pharmacology; Procyanidin C-1; Serum Albumin, Bovine - chemistry; Nanoparticles; Neuroinflammation; Blood-brain barrier; Alzheimer's disease; Procyanidin C-1
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.131739

Alzheimer's disease (AD) is a chronic neurodegenerative disease with high prevalence, long duration and poor prognosis. The blood-brain barrier (BBB) is a physiologic barrier in the central nervous system, which hinders the entry of most drugs into the brain from the blood, thus affecting the efficacy of drugs for AD. Natural products are recognized as one of the promising and unique therapeutic approaches to treat AD. To improve the efficiency and therapeutic effect of the drug across the BBB, a natural polyphenolic compound, procyanidin C-1 (C1) was encapsulated in glucose-functionalized bovine serum albumin (BSA) nanoparticles to construct Glu-BSA/C1 NPs in our study. Glu-BSA/C1 NPs exhibited good stability, slow release, biocompatibility and antioxidant properties. In addition, Glu-BSA/C1 NPs penetrated the BBB, accumulated in the brain by targeting Glut1, and maintained the BBB integrity both in vitro and in vivo. Moreover, Glu-BSA/C1 NPs alleviated memory impairment of 5 × FAD mice by reducing Aβ deposition and Tau phosphorylation and promoting neurogenesis. Mechanistically, Glu-BSA/C1 NPs significantly activated the PI3K/AKT pathway and inhibited the NLRP3/Caspase-1/IL-1β pathway thereby suppressing neuroinflammation. Taken together, Glu-BSA/C1 NPs could penetrate the BBB and mitigate neuroinflammation in AD, which provides a new therapeutic approach targeting AD. Schematic illustration of the synthesis and application of Glu-BSA/C1 NPs in a mouse model of Alzheimer's disease. [Display omitted]