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

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.