中国科学院高能物理研究所Liming Wang研究组经过不懈努力，阐明了蛋白冠的形状对其介导的纳米酶活性的抑制作用的影响。2024年4月5日出版的《美国化学会杂志》发表了这项成果。

据悉，在生物医学应用过程中，纳米酶表现出酶样特征，不可避免地与生命系统中的生物流体接触，导致其表面形成蛋白质冠。虽然都知道分子吸附可以影响纳米酶的催化活性，但对蛋白质冠对纳米酶活性的影响及其决定因素的了解还很缺乏。

为了解决这一空白，该研究团队采用AuNR@Pt@PDDAC [PDDAC，聚二烯基二甲基氯化铵]纳米棒(NR)作为具有多种活性的模型纳米酶，包括过氧化物酶、氧化酶和模拟过氧化氢酶的活性，研究蛋白质冠对催化活性的抑制作用。在对NR上血浆蛋白冠的主要成分进行鉴定后，课题组研究人员发现球形蛋白和纤维蛋白对纳米酶的催化活性有明显的抑制作用。

为了阐明其潜在的机制，该研究组发现吸附的蛋白质在纳米酶的表面组装，形成蛋白质网络(PNs)。值得注意的是，与球形蛋白形成的PNs相比，由纤维蛋白衍生的PNs具有较小孔径的筛网状结构。这种结构差异导致底物分子渗透效率降低，从而导致活性更明显的抑制。这些发现强调了蛋白质形状作为影响纳米酶活性的关键因素的重要性。这一发现为纳米酶在生物医学领域的合理设计和应用提供了有价值的见解。

附：英文原文

Title: Protein Corona-Mediated Inhibition of Nanozyme Activity: Impact of Protein Shape

Author: Yalin Cong, Rongrong Qiao, Xiaofeng Wang, Yinglu Ji, Jiacheng Yang, Didar Baimanov, Shengtao Yu, Rui Cai, Yuliang Zhao, Xiaochun Wu, Chunying Chen, Liming Wang

Issue&Volume: April 5, 2024

Abstract: During biomedical applications, nanozymes, exhibiting enzyme-like characteristics, inevitably come into contact with biological fluids in living systems, leading to the formation of a protein corona on their surface. Although it is acknowledged that molecular adsorption can influence the catalytic activity of nanozymes, there is a dearth of understanding regarding the impact of the protein corona on nanozyme activity and its determinant factors. In order to address this gap, we employed the AuNR@Pt@PDDAC [PDDAC, poly(diallyldimethylammonium chloride)] nanorod (NR) as a model nanozyme with multiple activities, including peroxidase, oxidase, and catalase-mimetic activities, to investigate the inhibitory effects of the protein corona on the catalytic activity. After the identification of major components in the plasma protein corona on the NR, we observed that spherical proteins and fibrous proteins induced distinct inhibitory effects on the catalytic activity of nanozymes. To elucidate the underlying mechanism, we uncovered that the adsorbed proteins assembled on the surface of the nanozymes, forming protein networks (PNs). Notably, the PNs derived from fibrous proteins exhibited a screen mesh-like structure with smaller pore sizes compared to those formed by spherical proteins. This structural disparity resulted in a reduced efficiency for the permeation of substrate molecules, leading to a more robust inhibition in activity. These findings underscore the significance of the protein shape as a crucial factor influencing nanozyme activity. This revelation provides valuable insights for the rational design and application of nanozymes in the biomedical fields.

DOI: 10.1021/jacs.3c14046

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.3c14046