ual-responsive SERS nanoprobe for real-time imaging of pH and ROS dynamics in wound healing
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- Key Laboratory of Emergency and Trauma, Ministry of Education, Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Haikou Trauma, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China
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- Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, Key Laboratory of Hainan Functional Materials and Molecular Imaging, Hainan Medical University, Haikou 571199, China
Received 3 October 2025, Revised 25 November 2025, Accepted 30 November 2025, Available online 2 December 2025, Version of Record 4 December 2025.
Volume 168, January 2026, 109325
https://doi.org/10.1016/j.bioorg.2025.109325
Highlights
•A dual-responsive SERS probe was developed for pH and ROS during wound healing.
•The probe integrated 4-MBA and DHBT on Au@Ag core–shell NPs for dual readouts.
•Real-time SERS imaging tracked inflammatory microenvironment changes in vivo.
•The probe exhibited high stability, low cytotoxicity, and broad pH responsiveness.
•SERS imaging enabled monitoring of wound status and therapeutic efficacy.
Abstract
In the complex process of wound healing, real-time and dynamic monitoring of key indicators such as pH and reactive oxygen species (ROS) in the microenvironment can effectively evaluate the inflammatory status and therapeutic effect of the wound. In this study, a dual-responsive surface-enhanced Raman scattering (SERS) probe was developed, which could simultaneously detect the changes of pH and ROS levels during the wound healing process. The gold–silver core–shell nanoparticles (Au@Ag NPs) were utilized as the active substrate, and 4-mercaptobenzoic acid (4-MBA) and 2,5-dihydroxythiophenol (DHBT) were modified as Raman reporter molecules, which were further coated with polyethylene glycol and bovine serum albumin to improve the biocompatibility and stability. In the Raman spectra, the peak of DHBT at 876 cm−1 was used to indicate the ROS level, while the intensity ratio at 1360 and 1075 cm−1 (I1360/I1075) of 4-MBA reflected the pH change. The SERS probe exhibited good ratiometric response characteristics, high selectivity, and low cytotoxicity. In vitro SERS imaging experiments demonstrated that the probe could dynamically monitor ROS generation and pH changes, while SERS imaging in the mouse wound model further confirmed its ability to monitor pH and ROS in the wound microenvironment in vivo. Histological analysis also verified its biosafety. In summary, the dual-responsive SERS probe designed in this study has potential application value in evaluating wound healing effects and provides a new approach for monitoring the wound microenvironment.
