Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China.
School of Chemistry and Environmental Engineering, Changchun University of Science and Technology, Changchun, Jilin, 130012, China.
Small. 2019 Jun;15(24):e1901116. doi: 10.1002/smll.201901116. Epub 2019 May 8.
The inhibition of amyloid-β (Aβ) aggregation by photo-oxygenation has become an effective way of treating Alzheimer's disease (AD). New near-infrared (NIR) activated treatment agents, which not only possess high photo-oxygenation efficiency, but also show low biotoxicity, are urgently needed. Herein, for the first time, it is demonstrated that NIR activated black phosphorus (BP) could serve as an effective nontoxic photo-oxidant for amyloid-β peptide in vitro and in vivo. The nanoplatform BP@BTA (BTA: one of thioflavin-T derivatives) possesses high affinity to the Aβ peptide due to specific amyloid selectivity of BTA. Importantly, under NIR light, BP@BTA can significantly generate a high quantum yield of singlet oxygen ( O ) to oxygenate Aβ, thereby resulting in inhibiting the aggregation and attenuating Aβ-induced cytotoxicity. In addition, BP could finally degrade into nontoxic phosphate, which guarantees the biosafety. Using transgenic Caenorhabditis elegans CL2006 as AD model, the results demonstrate that the O -generation system could dramatically promote life-span extension of CL2006 strain by decreasing the neurotoxicity of Aβ.
通过光氧化抑制淀粉样蛋白-β（Aβ）聚集已成为治疗阿尔茨海默病（AD）的有效方法。目前急需具有高光氧化效率且生物毒性低的新型近红外（NIR）激活治疗剂。本文首次证明，NIR 激活的黑磷（BP）可作为体外和体内淀粉样β肽的有效无毒光氧化剂。纳米平台 BP@BTA（BTA：噻唑蓝衍生物之一）由于 BTA 对 Aβ肽的特异性淀粉样选择性而对 Aβ肽具有高亲和力。重要的是，在近红外光下，BP@BTA 可以显著产生高量子产率的单线态氧（ 1 O 2 ）来氧化 Aβ，从而抑制其聚集并减弱 Aβ诱导的细胞毒性。此外，BP 最终可降解为无毒的磷酸盐，保证了生物安全性。利用转基因秀丽隐杆线虫 CL2006 作为 AD 模型，结果表明，O 2 生成系统通过降低 Aβ的神经毒性，可显著延长 CL2006 菌株的寿命。
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