​Ratiometric SERS imaging for indication of peroxynitrite fluctuations in diabetic wound healing process

Author links open overlay panelHui Chen【陈慧】 a b,Shanshan Lin【林珊珊】 a b,Dianqi Zhang【张点奇】 a b,Yanlong Xing【邢艳珑】 a b,Fabiao Yu 【于法标】a b,Rui Wang【王锐】 a b

• a

• Key Laboratory of Hainan Trauma and Disaster Rescue, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China

• b

• Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, Key Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Hainan Functional Materials and Molecular Imaging, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China

Received 27 March 2023, Revised 13 May 2023, Accepted 7 June 2023, Available online 8 June 2023, Version of Record 19 June 2023.

https://doi.org/10.1016/j.cej.2023.144024

Highlights

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  SERS nanoprobes were prepared through the Au@Ag core-ultrathin shell nanoparticles.

  
  

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  SERS nanoprobes could sensitively detect ONOO− in solution and living cells.

  
  

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  Dynamic fluctuations of ONOO− could be detected during the wound healing process

  
  

Abstract

Peroxynitrite (ONOO−) involves in diabetic wounds and its concentration is fluctuated in different pathological stages during the wound healing process. Thus, ONOO− may be utilized as a powerful biomarker to indicate the healing process of diabetic wound. However, the pathological roles of ONOO− can’t be fully understood yet. Herein, inspired by the mechanism that phenylboronic pinacol ester can react with ONOO− specifically, we report a new kind of SERS nanoprobes to monitor ONOO− fluctuation during diabetic wound healing process. The gold-silver (Au@Ag) core-ultrathin shell nanoparticles were utilized as active substrate and conjugated with phenylboronic pinacol ester molecules on the surface of Ag shell to simultaneously act as Raman reporter molecules and recognition moiety of ONOO−. In addition, functional polyethylene glycol (HS-PEG) and bovine serum albumin layers were sequentially immobilized on the surface of Ag shell to improve the stability of the nanoprobes. In the presence of ONOO−, phenylboronic pinacol ester could be converted into the corresponding phenol, inducing the SERS signal changes. The concentration fluctuation of ONOO− could be quantitatively detected through the SERS signal intensity ratio (1076 cm−1/998 cm−1) changes of typical peaks. The nanoprobes exhibited a wide response range from 0 to 75 μM with 0.12 μM as the detection limit. In the diabetic wound skin models, ONOO− concentration fluctuations during the wound healing process before and after drug treatment could be obtained by SERS imaging. We expect the proposed SERS imaging assay could be a noninvasive and powerful tool to monitor the diabetic wound healing.

Keywords

Surface-enhanced Raman scattering (SERS) imaging

Peroxynitrite fluctuation

Diabetes mellitus

Wound healing

Living cell and in vivo analysis

Scheme 1. Pathophysiology of diabetic wound healing and SERS detection of ONOO− for diabetic wound. (A) Systemic and (B) local diabetes-related physiological alternations in immune/ inflammatory response, cell/tissue function. (C) The reduced inflammatory response upon injury induces the chronic inflammation and lower tissue regeneration, especially the reaction oxygen species burst. (D) SERS detection of ONOO− in diabetic wound for healing monitoring. MФ, macrophage. The illustrations were created with the help of BioRender.com.