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卟啉基金属-有机骨架 PCN-224 纳米粒子用于近红外诱导的阿尔茨海默病淀粉样β肽聚集和神经毒性的衰减。

Porphyrinic Metal-Organic Framework PCN-224 Nanoparticles for Near-Infrared-Induced Attenuation of Aggregation and Neurotoxicity of Alzheimer's Amyloid-β Peptide.

机构信息

Department of Biomedical Engineering , The Hong Kong Polytechnic University , Hong Kong SAR , China.

Department of Mechanical and Automotive Engineering , Royal Melbourne Institute of Technology University , Melbourne , Victoria 3000 , Australia.

出版信息

ACS Appl Mater Interfaces. 2018 Oct 31;10(43):36615-36621. doi: 10.1021/acsami.8b15452. Epub 2018 Oct 19.

DOI:10.1021/acsami.8b15452
PMID:30338980
Abstract

The aberrant aggregation of amyloid-β peptide (Aβ) in the brain has been considered as the major pathological hallmark of Alzheimer's diseases (AD). Inhibition of Aβ aggregation is considered as an attractive therapeutic intervention for alleviating amyloid-associated neurotoxicity. Here, we report the near-infrared light (NIR)-induced suppression of Aβ aggregation and reduction of Aβ-induced cytotoxicity via porphyrinic metal-organic framework (MOF) PCN-224 nanoparticles. PCN-224 nanoparticles are hydrothermally synthesized by coordinating tetra-kis(4-carboxyphenyl)porphyrin (TCPP) ligands with zirconium. The PCN-224 nanoparticles show high photo-oxygenation efficiency, good biocompatibility, and high stability. The study reveals that the porphyrinic MOF-based nanoprobe activated by NIR light could successfully inhibit self-assembly of monomeric Aβ into a β-sheet-rich structure. Furthermore, photoexcited PCN-224 nanoparticles also significantly reduce Aβ-induced cytotoxicity under NIR irradiation.

摘要

淀粉样蛋白-β肽(Aβ)在大脑中的异常聚集被认为是阿尔茨海默病(AD)的主要病理标志。抑制 Aβ聚集被认为是缓解淀粉样相关神经毒性的一种有吸引力的治疗干预措施。在这里,我们通过卟啉金属-有机骨架(MOF)PCN-224 纳米粒子报告了近红外光(NIR)诱导的 Aβ聚集抑制和 Aβ诱导的细胞毒性降低。PCN-224 纳米粒子是通过将四-(4-羧基苯基)卟啉(TCPP)配体与锆配位水热合成的。PCN-224 纳米粒子具有高光氧效率、良好的生物相容性和高稳定性。研究表明,近红外光激活的基于卟啉 MOF 的纳米探针可以成功抑制单体 Aβ自组装成富含β-折叠的结构。此外,光激发的 PCN-224 纳米粒子在近红外照射下也能显著降低 Aβ诱导的细胞毒性。

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