期刊
CCS CHEMISTRY
卷 3, 期 8, 页码 2316-2330出版社
CHINESE CHEMICAL SOC
DOI: 10.31635/ccschem.020.202000468
关键词
soluble beta-amyloid aggregates; nanoscavengers; cross the BBB; coaggregate; microglial clearance
资金
- National Key Research and Development Programs of China [2018YFA0209700]
- National Natural Science Foundation of China (NSFC) [51673100, 21620102005]
- Fundamental Research Funds for the Central Universities (Nankai University) [ZB19100123, ZB16008705]
- Tianjin Natural Science Foundation [18JCQNJC03600]
- China Postdoctoral Science Foundation [2019M660975]
The novel nanoscavenger described in the study effectively clears soluble beta-amyloid aggregates, a key culprit in Alzheimer's disease progression. This nanoscavenger can cross the blood-brain barrier, enter the brain, and modulate biological processes to provide a new approach in nanomedicine development.
The accumulation of soluble beta-amyloid aggregates (sA beta s) is one of the main culprits in Alzheimer's disease (AD) progression, which can lead to synaptic dysfunction and subsequent neurodegeneration. Herein, we describe a nanoscavenger with novel structure that can cross the blood-brain barrier (BBB), accurately collect neurotoxic sA beta s, and facilitate amounts of beta-amyloid (A beta) clearance. The nanoscavenger is composed of an A beta-binding albumin nanoparticle surface-decorated with Immunoglobulin G (IgG) and brain-targeting peptide (PEGylated B6). During transport across the BBB, the nanoscavenger detaches PEGylated B6 and enters the brain. Then, the nanoscavenger competitively inhibits the formation of neurotoxic sA beta s, and induces the coaggregation of preexistent sA beta s, leading to the formation of nanoscavenger/A beta coaggregates. Such aggregates are readily cleared by microglia via antibody-dependent cell-mediated phagocytosis (ADCP) even under an inflammatory environment in APP/PS1 mice. Our nanoscavenger demonstrates a strategy to design a synthetic nanostructure to modulate disease-related biological processes, providing a new approach in nanomedicine development. [GRAPHICS] .
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