Extracellular deposition of β-amyloid (Aβ) peptide aggregates is a major characteristic of Alzheimer’s disease (AD) brain. Because Aβ peptide aggregates aggravate neuropathy and cognitive impairment for AD patients, numerous efforts have been devoted to suppressing Aβ self-assembly as a prospective AD treatment option. Here, we report Aβ-targeting, red-light-responsive carbon dots (CDs), and their therapeutic functions as a light-powered nanomodulator to spatiotemporally suppress toxic Aβ aggregation both in vitro and in vivo. Our aptamer-functionalized carbon dots (Apta@CDs) showed strong targeting ability toward Aβ₄₂ species. Moreover, red LED irradiation induced Apta@CDs to irreversibly denature Aβ peptides, impeding the formation of β-sheet-rich Aβ aggregates and attenuating Aβ-associated cytotoxicity. Consequently, Apta@CDs-mediated photomodualtion modality achieved effective suppression of Aβ aggregation in vivo, which significantly reduced the Aβ burden at the targeted sites in the brain of 5xFAD mice by ∼40% and ∼25% according to imaging and ELISA analyses, respectively. Our work demonstrates the therapeutic potential of photomodulating CDs for light-driven suppression against Aβ self-assembly and related neurotoxicity.

中文翻译：

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光调制碳点的时空抑制阿尔茨海默氏症的β淀粉样蛋白聚集。

β-淀粉样蛋白（Aβ）肽聚集体的细胞外沉积是阿尔茨海默病（AD）脑的主要特征。由于Aβ肽聚集会加剧AD患者的神经病变和认知功能障碍，因此人们已经做出了许多努力来抑制Aβ自组装作为一种潜在的AD治疗选择。在这里，我们报道了靶向Aβ的红光响应碳点（CDs），以及它们作为光动力纳米调节剂的治疗功能，可在体外和体内时空抑制有毒的Aβ聚集。我们的适体功能化碳点（Apta @ CD）对_Aβ42表现出强大的靶向能力种类。此外，红色LED辐射诱导Apta @ CDs不可逆地使Aβ肽变性，从而阻碍了富含β-折叠的Aβ聚集体的形成并减弱了Aβ相关的细胞毒性。因此，Apta @ CDs介导的光模态方式在体内可有效抑制Aβ聚集，根据成像和ELISA分析，其分别将5xFAD小鼠大脑目标部位的Aβ负担降低了约40％和〜25％。 。我们的工作证明了光调节CD对光驱动抑制Aβ自组装和相关神经毒性的治疗潜力。