Brazilin-Ce nanoparticles attenuate inflammation by de/anti-phosphorylation of IKKβ

Shengxuan Li; Kun Wang; Kai Jiang; Dongmei Xing; Ruhua Deng; Yue Xu; Yue Ding; Huida Guan; Lin-Lin Chen; Dandan Wang; Yang Chen; Wenbo Bu; Yaozu Xiang

doi:10.1016/j.biomaterials.2023.122466

Brazilin-Ce nanoparticles attenuate inflammation by de/anti-phosphorylation of IKKβ

Biomaterials. 2024 Mar:305:122466. doi: 10.1016/j.biomaterials.2023.122466. Epub 2024 Jan 5.

Authors

Shengxuan Li¹, Kun Wang², Kai Jiang¹, Dongmei Xing³, Ruhua Deng¹, Yue Xu¹, Yue Ding⁴, Huida Guan⁵, Lin-Lin Chen⁶, Dandan Wang¹, Yang Chen⁷, Wenbo Bu⁸, Yaozu Xiang⁹

Affiliations

¹ State Key Laboratory of Cardiology, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
² Department of Orthopedic Surgery, Spine Center, Changzheng Hospital, The Second Military Medical University, Shanghai, 200003, China.
³ The First Affiliated Hospital of Henan University of Chinese Medicine, Heart Center/National Regional (Traditional Chinese Medicine) Cardiovascular Diagnosis and Treatment Center, Zhengzhou, 450000, Henan, China.
⁴ School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
⁵ Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
⁶ Key Laboratory of Chinese Medicine Resource and Compound Prescription, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, 430065, China.
⁷ Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, School of Life Sciences and Technology, Shanghai Fourth People's Hospital, Tongji University, Shanghai, 200434, China. Electronic address: chenyanglg@tongji.edu.cn.
⁸ Department of Materials Science and State Key Laboratory of Molecular Engineering of Polymers, Academy for Engineering and Technology, Fudan University, Shanghai, 200433, China. Electronic address: wbbu@fudan.edu.cn.
⁹ State Key Laboratory of Cardiology, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China; Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, School of Life Sciences and Technology, Shanghai Fourth People's Hospital, Tongji University, Shanghai, 200434, China. Electronic address: yaozu.xiang@tongji.edu.cn.

PMID: 38184960
DOI: 10.1016/j.biomaterials.2023.122466

Abstract

Inflammation is associated with a series of diseases like cancer, cardiovascular disease and infection, and phosphorylation/dephosphorylation modification of proteins are important in inflammation regulation. Here we designed and synthesized a novel Brazilin-Ce nanoparticle (BX-Ce NPs) using Brazilin, which has been used for anti-inflammation in cardiovascular diseases but with narrow therapeutic window, and Cerium (IV), a lanthanide which has the general activity in catalyzing the hydrolysis of phosphoester bonds, to conferring de/anti-phosphorylation of IKKβ. We found that BX-Ce NPs specifically bound to Asn225 and Lys428 of IKKβ and inhibited its phosphorylation at Ser181, contributing to appreciably anti-inflammatory effect in cellulo (IC₅₀ = 2.5 μM). In vivo mouse models of myocardial infarction and sepsis also showed that the BX-Ce NPs significantly ameliorated myocardial injury and improved survival in mice with experimental sepsis through downregulating phosphorylation of IKKβ. These findings provided insights for developing metal nanoparticles for guided ion interfere therapy, particularly synergistically target de/anti-phosphorylation as promising therapeutic agents for inflammation and related diseases.

Keywords: Anti-inflammation; Brazilin-Cerium nanoparticles; De/anti-phosphorylation; Guided ion interference therapy; Myocardial infarction.

MeSH terms

Animals
Benzopyrans*
Cerium* / chemistry
I-kappa B Kinase / metabolism
I-kappa B Kinase / therapeutic use
Inflammation / drug therapy
Metal Nanoparticles* / therapeutic use
Mice
Nanoparticles* / chemistry
Phosphorylation
Sepsis*

Substances

I-kappa B Kinase
brazilin
Cerium
Benzopyrans