Carbon Monoxide Controllable Targeted Gas Therapy for Synergistic Anti-inflammation.

Xiaogang Qu,Zhi Du,Yuhuan Sun,Jinsong Ren,Mengmeng Ma,Chun Liu

doi:10.1016/j.isci.2020.101483

Abstract

SummaryCarbon monoxide (CO) plays an important role in the regulation of a variety of physiological processes and thus is regarded as a promising pharmaceutical agent. Nevertheless, therapeutic applications of CO are severely hampered by the difficulty of the delivery of controlled amounts of CO to biological targets. To address this deficiency, we present a spatiotemporally controllable CO-releasing platform (designated as Neu-MnO2/Fla) for synergistic anti-inflammation. With the assistance of neutrophil membrane coating, Neu-MnO2/Fla can target to inflammatory sites. Subsequently, excess H2O2 at the inflamed tissues can be decomposed into oxygen because of MnO2 as nanozymes possessing catalase (CAT) activity, which not only relieves oxidative stress but also achieves in situ rapid photo-induced CO release. The in vitro and in vivo results indicate our CO-releasing platform exhibits a strong synergistic anti-inflammatory effect. Our work will shed light on targeted CO release to avoid side effects of therapeutic applications of CO.

Highlights

In order to verify our hypothesis, the Neu-MnO2/Fla were synthesized by embedding Fla into the hollow mesoporous MnO2 nanoparticles and further coating them with neutrophil membrane
Dynamic light scattering (DLS) demonstrated the hydrodynamic diameters of MnO2 increased after neutrophil membrane coating (Figure S3)
The Fourier transform infrared (FTIR) spectrum and X-ray photoelectron spectroscopy (XPS) analysis indicated the preparation of MnO2 (Figures S4 and S5)

Summary

Introduction

The emerging researches of carbon monoxide (CO) gas therapy have attracted widespread attention, including therapy of neurodegenerative diseases (Queiroga et al, 2015) and as an antibacterial (Wareham et al, 2015), anti-cancer (Wegiel et al, 2013; Wu et al, 2018a), and especially anti-inflammatory agent (He et al, 2015; Ji et al, 2016b; Popova et al, 2018; Zheng et al, 2018; Wang et al, 2019). The clinical application of inhaled CO presents several disadvantages, including lack of tissue specificity, difficulty in controlling precise amounts, and the need for complex hospital devices (Ji et al, 2016a). To overcome these limitations, many CO-releasing molecules (CORMs) have been developed as non-gaseous forms of CO delivery (Mann, 2012; Heinemann et al, 2014; Garcia-Gallego and Bernardes, 2014; Chakraborty et al, 2014; Chaves-Ferreira et al, 2015). Berreau’s group reported a flavonol-based organic CORM, 3-hydroxybenzo [g]flavone (Fla), featuring the capacities of fluorescence traceability in cells, low toxicity, and CO release in the presence of oxygen and the light (Popova et al, 2018; Anderson et al, 2015; Soboleva et al, 2017)

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Conclusion