CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics Chinese Academy of Science, Dalian 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China.
CAS Key Laboratory of Separation Science for Analytical Chemistry, National Chromatographic R. & A. Center, Dalian Institute of Chemical Physics Chinese Academy of Science, Dalian 116023, China; The Research Center for Medical Genomics, Key Laboratory of Medical Cell Biology, Ministry of Education, School of Life Science, China Medical University, Shenyang, Liaoning Province 110001, China.
Acta Biomater. 2023 Mar 1;158:673-685. doi: 10.1016/j.actbio.2022.12.069. Epub 2023 Jan 9.
Relatively low catalytic activity and poor targeting limit the applications of nanoceria (CeO) nanozymes in the treatment of tumors. Here, we designed a unique pushpin-like Au/CeO hybrid nanozyme with high catalytic activity by combining site-selective growth and steric restriction strategies. The enhanced enzyme activity was attributed to plasmon-induced hot electrons. Furthermore, the pushpin-like structure facilitated targeting molecule modification. The nanozyme exhibited superior antitumor effects both in vitro and in vivo due to its high catalytic activity and targeting effects. Importantly, its potential mechanism of anti-tumor therapy was studied by quantitative proteomics. The reactive oxygen species (ROS) generated by folic acid-PEG thiol-Au/CeO (FA-Au/CeO) caused mitochondrial and proteasomal damage in tumor cells and further evoked a response to oxidative stress and innate immunity in vivo. This study provided a spatiotemporal approach to enhance the antitumor activity of nanozymes by structural design. The designed pushpin-like Au/CeO could be utilized as a multifunctional nanoplatform for in vitro and in vivo plasmon-enhanced cancer therapy with active targeting effects. Moreover, this study systematically explored the anti-tumor mechanism of the nanozyme in both cell and mouse models, promoting its translation to the clinic. STATEMENT OF SIGNIFICANCE: A strategy combining the principles of site-selective growth and steric restriction was developed to prepare a unique pushpin-like Au/CeO hybrid nanozyme with high catalytic activity and low steric hindrance. The hybrid nanozyme showed superior antitumor activity at both the cellular and tissue levels. Furthermore, the antitumor mechanism was investigated in terms of the differential proteins and their pathways using quantitative proteomics, thus promoting the translation of nanozymes to the clinic.
相对较低的催化活性和较差的靶向性限制了纳米氧化铈（CeO）纳米酶在肿瘤治疗中的应用。在这里，我们通过结合位点选择性生长和空间位阻策略，设计了一种具有高催化活性的独特的别针状 Au/CeO 杂化纳米酶。增强的酶活性归因于等离子体诱导的热电子。此外，别针状结构有利于靶向分子的修饰。由于其高催化活性和靶向作用，该纳米酶在体外和体内均表现出优异的抗肿瘤效果。重要的是，通过定量蛋白质组学研究了其抗肿瘤治疗的潜在机制。叶酸-PEG 巯基-Au/CeO（FA-Au/CeO）产生的活性氧（ROS）导致肿瘤细胞中线粒体和蛋白酶体损伤，并进一步在体内引发氧化应激和固有免疫反应。这项研究通过结构设计提供了一种时空方法来增强纳米酶的抗肿瘤活性。设计的别针状 Au/CeO 可作为一种多功能纳米平台，用于体外和体内等离子体增强癌症治疗，并具有主动靶向作用。此外，本研究系统地研究了纳米酶在细胞和小鼠模型中的抗肿瘤机制，促进了其向临床的转化。
开发了一种结合位点选择性生长和空间位阻原理的策略，制备了具有高催化活性和低空间位阻的独特别针状 Au/CeO 杂化纳米酶。该杂化纳米酶在细胞和组织水平均表现出优异的抗肿瘤活性。此外，通过定量蛋白质组学研究了抗肿瘤机制，从而促进了纳米酶向临床的转化。
