Department of Rehabilitation Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China.
Department of Medical Ultrasound, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, China.
J Nanobiotechnology. 2022 Jul 14;20(1):322. doi: 10.1186/s12951-022-01524-4.
BACKGROUND: 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. RESULTS: 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 β-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 β-amyloid plaques which more closely revealed real deposition of Aβ 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. CONCLUSIONS: Gathered data demonstrated that this theranostic platform may have both early diagnostic and therapeutic potential in AD.
背景:阿尔茨海默病(AD)是最常见的神经退行性疾病,目前尚无有效的治疗方法,也缺乏针对临床前 AD 患者的诊断策略。因此,迫切需要开发 AD 的早期诊断和治疗干预方法。
结果:在此,我们开发了一种纳米诊疗平台,该平台由姜黄素(Cur)、抗炎分子和超顺磁性氧化铁(SPIO)纳米粒子组成,这些纳米粒子被二嵌段 1,2-二油酰基-sn-甘油-3-磷酸乙醇胺-n-[聚(乙二醇)](DSPE-PEG)包裹,并在其表面修饰 CRT 和 QSH 肽。此外,我们证明这种多功能纳米材料可有效减少 APP/PS1 转基因小鼠中β-淀粉样斑块的负担,其过程可通过磁共振成像(MRI)进行非侵入性检测,并将二维 MRI 图像计算成三维(3D)图谱。我们的数据表明,该方法能够高度灵敏地检测体内β-淀粉样斑块,比以前报道的方法更能真实地揭示 Aβ的沉积情况,并且我们首次基于 3D 图谱定量了斑块的体积。此外,还显著改善了小鼠的记忆缺陷,这可能与抑制 NOD 样受体家族含pyrin 结构域蛋白 3(NLRP3)炎性小体有关。
结论:综合数据表明,这种治疗平台可能具有 AD 的早期诊断和治疗潜力。
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