Nanobiointeractions & Nanodiagnostics, Istituto Italiano di Tecnologia (IIT), Via Morego 30, 16163 Genova, Italy.
Department of Chemistry and Industrial Chemistry, University of Genova, Via Dodecaneso 31, 16146 Genova, Italy.
Nano Lett. 2023 May 24;23(10):4660-4668. doi: 10.1021/acs.nanolett.3c01479. Epub 2023 May 8.
Oxidative stress is known to be the cause of several neurovascular diseases, including neurodegenerative disorders, since the increase of reactive oxygen species (ROS) levels can lead to cellular damage, blood-brain barrier leaking, and inflammatory pathways. Herein, we demonstrate the therapeutic potential of 5 nm platinum nanoparticles (PtNPs) to effectively scavenge ROS in different cellular models of the neurovascular unit. We investigated the mechanism underlying the PtNP biological activities, analyzing the influence of the evolving biological environment during particle trafficking and disclosing a key role of the protein corona, which elicited an effective switch-off of the PtNP catalytic properties, promoting their selective activity. Upon cellular internalization, the lysosomal environment switches on and boosts the enzyme-like activity of the PtNPs, acting as an intracellular "catalytic microreactor" exerting strong antioxidant functionalities. Significant ROS scavenging was observed in the neurovascular cellular models, with an interesting protective mechanism of the Pt-nanozymes along lysosomal-mitochondrial axes.
氧化应激是几种神经血管疾病（包括神经退行性疾病）的原因，因为活性氧（ROS）水平的增加会导致细胞损伤、血脑屏障渗漏和炎症途径。在此，我们证明了 5nm 铂纳米粒子（PtNPs）在神经血管单元的不同细胞模型中有效清除 ROS 的治疗潜力。我们研究了 PtNP 生物学活性的潜在机制，分析了在颗粒运输过程中不断变化的生物环境的影响，并揭示了蛋白质冠的关键作用，它有效地关闭了 PtNP 的催化特性，促进了其选择性活性。在细胞内化后，溶酶体环境启动并增强了 PtNPs 的酶样活性，充当细胞内“催化微反应器”，发挥强大的抗氧化功能。在神经血管细胞模型中观察到显著的 ROS 清除，Pt-纳米酶沿着溶酶体-线粒体轴表现出有趣的保护机制。
