Pushpin-like nanozyme for plasmon-enhanced tumor targeted therapy

Baofu Ma; Kun Zhang; Zhen Sun; Hui Pan; Kaiguang Yang; Bo Jiang; Baofeng Zhao; Zhen Liang; Yukui Zhang; Lihua Zhang

doi:10.1016/j.actbio.2022.12.069

Pushpin-like nanozyme for plasmon-enhanced tumor targeted therapy

Acta Biomater. 2023 Mar 1:158:673-685. doi: 10.1016/j.actbio.2022.12.069. Epub 2023 Jan 9.

Authors

Baofu Ma¹, Kun Zhang², Zhen Sun³, Hui Pan¹, Kaiguang Yang⁴, Bo Jiang⁵, Baofeng Zhao⁶, Zhen Liang⁴, Yukui Zhang⁴, Lihua Zhang⁷

Affiliations

¹ 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.
² 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.
³ Department of Oncology, The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Affiliated Zhongshan Hospital of Dalian University, No. 6 Jie fang Street, Dalian, Liaoning 110006, China.
⁴ 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.
⁵ 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. Electronic address: [email protected].
⁶ 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. Electronic address: [email protected].
⁷ 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. Electronic address: [email protected].

PMID: 36632878
DOI: 10.1016/j.actbio.2022.12.069

Abstract

Relatively low catalytic activity and poor targeting limit the applications of nanoceria (CeO₂) nanozymes in the treatment of tumors. Here, we designed a unique pushpin-like Au/CeO₂ 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/CeO₂ (FA-Au/CeO₂) 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/CeO₂ 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/CeO₂ 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.

Keywords: Cancer therapy; Nanoceria nanozyme; Plasmon-enhanced catalysis; Pushpin-like; Quantitative proteomics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Catalysis
Mice
Neoplasms* / drug therapy
Reactive Oxygen Species / metabolism

Substances

Reactive Oxygen Species