"Cascaded Rocket" Nanosystems with Spatiotemporal Separation for Triple-Synergistic Therapy of Alzheimer's Disease
文献类型：期刊论文
| 作者 | Liu, Ruiyuan1,2,3; Yang, Jun1,2; Qiu, Xinyu1; Ji, Weihong1,2; Shen, Jie1,2; Li, Yan1,2; Lu, Zhiguo1,2; Wu, Yanyue1,2; Wang, Wenli1; Wang, Jing4 |
| 刊名 | ADVANCED HEALTHCARE MATERIALS
 |
| 出版日期 | 2022-02-24 |
| 页码 | 10 |
| ISSN号 | 2192-2640 |
| 关键词 | Alzheimer's disease cascaded rockets metal ion enzyme responses spatiotemporal separation |
| DOI | 10.1002/adhm.202101748 |
| 英文摘要 | Alzheimer's disease (AD) remains an incurable disease due to the intricate pathogenesis. The neuropathological hallmarks include extracellular amyloid-beta (A beta) plaques, tau phosphorylation and extensive oxidative stress in neurons, which facilitate the progression of AD. Based on the complex etiology, a spatiotemporally "cascaded rocket" delivery system (DPH/TPGAS NPs) with metal ion/enzyme responses is established in this study for triple-synergistic AD treatment. After targeting and permeating the blood-brain barrier (BBB), the histidine units in the DPH chelate excess metal ions at the extracellular microenvironment, restraining the formation of A beta aggregates, inducing the first-stage separation. Then, the remanent system targets neuronal cells and triggers the second separation with cathepsin B for reducing the level of phosphorylated tau and oxidative stress. Accordingly, the DPH/TPGAS NPs can achieve spatiotemporal drug release, which results in enhanced synergistic therapeutic effects both in the extracellular and intracellular region of the AD brain. After treating with DPH/TPGAS NPs, the memory deficits, levels of A beta and phosphorylated tau, inflammation and neuron damages are remarkably ameliorated in 3 x Tg-AD mice. Therefore, this "cascaded rocket" delivery system has great potential to serve as a powerful platform and provides a new horizon to the therapeutic strategy for AD and other brain diseases' treatments. |
| WOS关键词 | TAU-MEDIATED NEURODEGENERATION ; OXIDATIVE STRESS ; NANOPARTICLES ; MICROGLIA ; HISTIDINE ; DELIVERY |
| 资助项目 | National Natural Science Foundation of China[22075289] ; National Natural Science Foundation of China[31771095] ; National Natural Science Foundation of China[21875254] ; National Natural Science Foundation of China[21905283] ; National Natural Science Foundation of China[52073287] ; National Natural Science Foundation of China[32071391] ; National High Technology Research and Development Program[2016YFA0200303] ; Beijing Natural Science Foundation[L172046] ; Beijing Natural Science Foundation[2192057] |
| WOS研究方向 | Engineering ; Science & Technology - Other Topics ; Materials Science |
| 语种 | 英语 |
| 出版者 | WILEY |
| WOS记录号 | WOS:000760130600001 |
| 资助机构 | National Natural Science Foundation of China ; National High Technology Research and Development Program ; Beijing Natural Science Foundation |
| 源URL | [http://ir.ipe.ac.cn/handle/122111/52084]  |
| 专题 | 中国科学院过程工程研究所 |
| 通讯作者 | Zhang, Xin |
| 作者单位 | 1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Heze Univ, Coll Pharm, Heze 274015, Peoples R China 4.Hebei Med Univ, Hebei Prov Key Lab Innovat Drug Res & Evaluat, Sch Pharm, Shijiazhuang 050017, Hebei, Peoples R China 5.Shandong First Med Univ & Shandong Acad Med Sci, Coll Pharm, Tai An 271000, Shandong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Ruiyuan,Yang, Jun,Qiu, Xinyu,et al. "Cascaded Rocket" Nanosystems with Spatiotemporal Separation for Triple-Synergistic Therapy of Alzheimer's Disease[J]. ADVANCED HEALTHCARE MATERIALS,2022:10. |
| APA | Liu, Ruiyuan.,Yang, Jun.,Qiu, Xinyu.,Ji, Weihong.,Shen, Jie.,...&Zhang, Xin.(2022)."Cascaded Rocket" Nanosystems with Spatiotemporal Separation for Triple-Synergistic Therapy of Alzheimer's Disease.ADVANCED HEALTHCARE MATERIALS,10. |
| MLA | Liu, Ruiyuan,et al.""Cascaded Rocket" Nanosystems with Spatiotemporal Separation for Triple-Synergistic Therapy of Alzheimer's Disease".ADVANCED HEALTHCARE MATERIALS (2022):10. |
入库方式： OAI收割
来源：过程工程研究所
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