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铂纳米酶在氧化应激介导的疾病模型中恢复细胞活性氧稳态。

Platinum nanozymes recover cellular ROS homeostasis in an oxidative stress-mediated disease model.

作者信息

Moglianetti Mauro, De Luca Elisa, Pedone Deborah, Marotta Roberto, Catelani Tiziano, Sartori Barbara, Amenitsch Heinz, Retta Saverio Francesco, Pompa Pier Paolo

机构信息

Istituto Italiano di Tecnologia, Center for Biomolecular Nanotechnologies, Via Barsanti - 73010 Arnesano, Lecce, Italy.

出版信息

Nanoscale. 2016 Feb 14;8(6):3739-52. doi: 10.1039/c5nr08358c. Epub 2016 Jan 27.

Abstract

In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide dismutase, catalase, and peroxidase enzymes, with similar or even superior performance than natural enzymes, along with higher adaptability to the changes in environmental conditions. We then exploited their potent activity as radical scavenging materials in a cellular model of an oxidative stress-related disorder, namely human Cerebral Cavernous Malformation (CCM) disease, which is associated with a significant increase in intracellular ROS levels. Noteworthily, we found that Pt nanozymes can efficiently reduce ROS levels, completely restoring the cellular physiological homeostasis.

摘要

近年来,使用纳米材料作为仿生酶引起了极大的兴趣。在这项工作中,我们展示了生物相容性铂纳米颗粒(Pt NPs)作为抗氧化纳米酶的潜力,其兼具丰富的细胞内化能力和高效清除细胞活性氧(ROS)的活性,从而同时整合了纳米载体和抗氧化药物的功能。对Pt NPs进行仔细的毒性评估和细胞内追踪,证明了它们的细胞相容性和高细胞摄取率,且在内吞/溶酶体囊泡中存在区室化现象。我们已经证明,Pt NPs具有强大且广泛的抗氧化特性,可作为超氧化物歧化酶、过氧化氢酶和过氧化物酶发挥作用,其性能与天然酶相似甚至更优,同时对环境条件变化具有更高的适应性。然后,我们在一种与氧化应激相关的疾病——人类脑海绵状血管畸形(CCM)疾病的细胞模型中,利用它们作为自由基清除材料的强大活性,该疾病与细胞内ROS水平的显著升高有关。值得注意的是,我们发现Pt纳米酶可以有效降低ROS水平,完全恢复细胞的生理稳态。

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