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Five major reactive oxygen species (ROS) are generated in diseases including H2O2, •OH, O2 •-, ROO•, and 1O2. Simultaneous detection of the five ROS with a single probe is crucial for a comprehensive understanding of the development and progression of many diseases, such as cancer and inflammatory diseases. However, currently reported detection systems are limited by targeting one ROS with one probe. This one-to-one detection mode may fail to sufficiently unveil the diseased state. In this study, we achieved simultaneous detection of all the five ROS with one probe (i.e., one-to-all detection), by designing a novel para-aminothiophenol (PATP) and hemin-decorated gold (Au/PATP/Hemin) nanoprobe. The design is principled by our discovery that PATP can react with •OH, O2 •-, ROO•, and 1O2 by a radical oxidative coupling mechanism to form 4,4′-dimercaptoazobenzene (DMAB). The DMAB then elicited strong characteristic surface-enhanced Raman scattering (SERS) peaks at 1142, 1386, and 1432 cm-1 which in turn enables direct detection of •OH, O2 •-, ROO•, and 1O2 and indirect detection of H2O2 by hemin-catalyzed fenton reaction to convert H2O2 into •OH. In two representative ROS-elevated mice models of tumors and allergic dermatitis, the Au/PATP/Hemin nanoprobe demonstrated its robust performance of monitoring tumor development and inflammation progression in a highly sensitive and quantitative manner.

Quan Qi,1,* Lei Lu,2,3,* Haiqing Li,1,* Zhize Yuan,1 Gaoxian Chen,2,3 Miao Lin,2,3 Zhengwen Ruan,4 Xiaofeng Ye,1 Zeyu Xiao,2,3,5 Qiang Zhao1 1Department of Cardiac Surgery, Rui Jin Hospital, 2Department of Pharmacology, Institute of Medical Sciences, 3Translational Medicine Collaborative Innovation Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 4Department of Cardiology, Yuyao People’s Hospital, Yuyao, Zhejiang, 5Collaborative Innovation Center of Systems Biomedicine, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: The local, intramyocardial injection of proteins into the infarcted heart is an attractive option to initiate cardiac regeneration after myocardial infarction (MI). Liraglutide, which was developed as a treatment for type 2 diabetes, has been implicated as one of the most promising protein candidates in cardiac regeneration. A significant challenge to the therapeutic use of this protein is its short half-life in vivo. In this study, we evaluated the therapeutic effects and long-term retention of liraglutide loaded in poly(lactic-co-glycolic acid)–poly(ethylene glycol) (PLGA–PEG) nanoparticles (NP-liraglutide) on experimental MI. PLGA–PEG nanoparticles (NPs) have been shown to efficiently load liraglutide and release bioactive liraglutide in a sustained manner. For in vitro test, the released liraglutide retained bioactivity, as measured by its ability to activate liraglutide signaling pathways. Next, we compared the effects of an intramyocardial injection of saline, empty NPs, free liraglutide and NP-liraglutide in a rat model of MI. NPs were detected in the myocardium for up to 4 weeks. More importantly, an intramyocardial injection of NP-liraglutide was sufficient to improve cardiac function (P<0.05), attenuate the infarct size (P<0.05), preserve wall thick