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Mitochondrial SO2-Activated NIR Photodiagnostic Agent Harnessing Hydroxyl Radicals for Efficient Inflammation
Yingcui Bu1, Yingyu Zhu1, Yuxin Yang2
1School of Materials and Chemistry, Anhui Agricultural University, 230036 Hefei, P.R. China.
Abstract:
At present, some progress has been made in developing NIR light-responsive free radical generators. However, the efficacy of theranostics continues to be hindered by tumor-associated inflammatory reactions. Hence, fulfilling the in situ release of free radicals upon NIR light excitation specifically activated by the inflammation microenvironment would be an ideal strategy for efficient inflammation eradication and tumor suppression but remains a challenge. Herein, a SO2 (overexpressed reactive sulfur species in inflamed site)-stimulated phototheranostic agent (CVS) is successfully developed. Through a specific response to both endogenous and exogenous SO2 with a low LOD (31.7 nM), CVS demonstrates the "switch on" two-photon activity as well as efficient OH· generation. Remarkably, in CVS-treated H22-tumor-bearing mice, the NIR light-activated accurate inflammation eradication and tumor suppression are accomplished. This reactive phototheranostic platform not only facilitates the quantification of SO2 during inflammation but also renders it a potent NIR antihypoxic tumor agent.
Insights
A novel phototheranostic agent (CVS) releases free radicals upon near-infrared (NIR) light activation, specifically targeting inflammation. This approach effectively eradicates inflammation and suppresses tumors by leveraging sulfur dioxide (SO2) in the tumor microenvironment.
Area of Science:
- Biomedical Engineering
- Chemical Biology
- Oncology
Background:
- Theranostics face challenges due to tumor-associated inflammation, hindering efficacy.
- Existing near-infrared (NIR) light-responsive free radical generators require improved specificity.
- Targeting inflammation-specific triggers is crucial for advanced cancer theranostics.
Purpose of the Study:
- To develop a novel phototheranostic agent activated by inflammation-specific cues.
- To create an agent capable of in situ free radical generation upon NIR light excitation.
- To investigate the agent's efficacy in inflammation eradication and tumor suppression.
Main Methods:
- Development of a sulfur dioxide (SO2)-stimulated phototheranostic agent (CVS).
- Evaluation of CVS's response to endogenous and exogenous SO2 with low limit of detection (LOD).
- Assessment of two-photon activity and hydroxyl radical (OH·) generation.
- In vivo studies using H22-tumor-bearing mice treated with CVS and NIR light.
Main Results:
- CVS demonstrated a specific response to SO2 with a low LOD of 31.7 nM.
- The agent exhibited 'switch on' two-photon activity and efficient OH· generation.
- NIR light-activated inflammation eradication and tumor suppression were achieved in vivo.
- The platform enabled SO2 quantification and acted as an anti-hypoxic agent.
Conclusions:
- A novel SO2-stimulated phototheranostic agent (CVS) was successfully developed.
- CVS offers a targeted approach for inflammation-specific phototherapy and tumor suppression.
- This platform provides a potential tool for SO2 detection and NIR antihypoxic cancer therapy.
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