Highly sensitive Curcumin-conjugated nanotheranostic platform for detecting amyloid-beta plaques by magnetic resonance imaging and reversing cognitive deficits of Alzheimer's disease via NLRP3-inhibition

• Published in: Journal of nanobiotechnology Vol. 20; no. 1; pp. 1 - 322
• Main Authors: Ruan, Yuting, Xiong, Ying, Fang, Wenli, Yu, Qun, Mai, Yingren, Cao, Zhiyu, Wang, Kexi, Lei, Ming, Xu, Jiaxin, Liu, Yan, Zhang, Xingcai, Liao, Wang, Liu, Jun
• Format: Journal Article
• Language: English
• Published: London BioMed Central Ltd 14.07.2022; BioMed Central; BMC
• Subjects: Acids; Alzheimer's disease; Amyloid beta-protein; Antibodies; Binding sites; Care and treatment; Cognitive ability; Curcumin; Development and progression; Diagnosis; Health aspects; Hemodialysis; Inflammasomes; Inflammation; Inhibition (psychology); Intracranial pressure; Iron oxides; Magnetic resonance imaging; Mass spectrometry; Medical imaging; Medical research; Morphology; Nanomaterials; Nanoparticles; Nanotheranostics; Neurodegenerative diseases; Nitrogen; NLRP3 inflammasome; Peptides; Polyethylene glycol; Presenilin 1; Pyrin protein; Radiation; Resonance; Scientific imaging; Senile plaques; Transgenic mice; Turmeric; β-Amyloid; China; United States > US; Japan
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-022-01524-4

Alzheimer's disease (AD) is the most common neurodegenerative disorder without effective therapy and lack diagnosis strategy for preclinical AD patients. There is an urgent need for development of both early diagnosis and therapeutic intervention of AD. Herein, we developed a nanotheranostics platform consisting of Curcumin (Cur), an anti-inflammatory molecule, and superparamagnetic iron oxide (SPIO) nanoparticles encapsulated by diblock 1,2-dio-leoyl-sn-glycero-3-phosphoethanolamine-n-[poly(ethylene glycol)] (DSPE-PEG) that are modified with CRT and QSH peptides on its surface. Furthermore, we demonstrated that this multifunctional nanomaterial efficiently reduced [beta]-amyloid plaque burden specifically in APP/PS1 transgenic mice, with the process noninvasively detected by magnetic resonance imaging (MRI) and the two-dimensional MRI images were computed into three-dimension (3D) plot. Our data demonstrated highly sensitive in vivo detection of [beta]-amyloid plaques which more closely revealed real deposition of A[beta] than previously reported and we quantified the volumes of plaques for the first time based on 3D plot. In addition, memory deficits of the mice were significantly rescued, probably related to inhibition of NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasomes. Gathered data demonstrated that this theranostic platform may have both early diagnostic and therapeutic potential in AD.