Key Takeaways & Executive Findings
- •• • The nanoprobe CPPO@TN NPs exhibits NIR chemiluminescence with a signal-to-noise ratio sufficient for in vivo imaging of drug-induced liver injury and peritonitis, achieving high sensitivity and specificity in murine models. • • The system generates sustained singlet oxygen (1O2) production without external irradiation, enabling effective photodynamic therapy; in a 4T1 tumor-bearing mouse model, tumor growth was significantly inhibited. • • Co-encapsulation of CPPO, AIE photosensitizer TN, and soybean oil within F-127 micelles ensures a persistent CIEEL process, providing prolonged chemiluminescence and 1O2 generation for theranostic applications. • • The nanoprobe operates without external light excitation, eliminating tissue autofluorescence and photobleaching, thereby improving imaging fidelity and therapeutic safety in deep-tissue applications.
Abstract
Real-time, in situ imaging of hydrogen peroxide (H2O2), a key reactive oxygen species implicated in various diseases, remains challenging due to limitations of existing probes, such as short emission wavelengths and reliance on external excitation. To address these issues, we developed an H2O2-triggered near-infrared (NIR) chemiluminescence (CL) nanoprobe with aggregation-induced emission (AIE) characteristics for in vivo inflammation imaging and tumor theranostics. This nanoprobe, denoted as CPPO@TN NPs, was constructed by co-encapsulating a tailored AIE photosensitizer (TN) with strong NIR emission and high singlet oxygen (1O2) generation, a H2O2-responsive chemiluminescent substrate (CPPO), and soybean oil (as a retarder) within F-127 micelles. Upon encountering H2O2, the nanoprobe undergoes a persistent chemically initiated electron exchange luminescence (CIEEL) process that activates AIEgens, resulting in intense NIR chemiluminescence and sustained 1O2 production without the need for external irradiation. Leveraging this mechanism, CPPO@TN NPs achieved highly sensitive and specific imaging of drug-induced liver injury and peritonitis in murine models, with exceptional tissue penetration and signal-to-noise ratio. Furthermore, the nanoprobe facilitated effective self-luminescent imaging and photodynamic therapy of tumors, significantly inhibiting tumor growth in a 4T1 tumor-bearing mouse model. This platform provides an external light excitation-free theranostic strategy for H2O2-associated diseases.
1. Introduction
Hydrogen peroxide (H2O2) is a critical reactive oxygen species (ROS) involved in numerous physiological and pathological processes, including inflammation, cancer, and neurodegenerative diseases. Elevated H2O2 levels are hallmarks of these conditions, making its detection and imaging essential for both understanding disease mechanisms and developing diagnostic and therapeutic strategies. Conventional fluorescence imaging, while offering high spatiotemporal resolution, relies on external light excitation, which induces tissue autofluorescence, reduces signal-to-background ratio, and causes photobleaching and phototoxicity, limiting long-term in vivo applications. Chemiluminescence (CL) imaging, which generates light through chemical reactions, eliminates the need for external excitation, thereby overcoming these limitations. However, existing CL probes often suffer from short emission wavelengths and low efficiency, hindering deep-tissue imaging.
To address these bottlenecks, we developed a H2O2-triggered NIR chemiluminescence nanoprobe with aggregation-induced emission (AIE) properties. The nanoprobe, CPPO@TN NPs, integrates a tailored AIE photosensitizer (TN) with strong NIR emission and high singlet oxygen generation, a H2O2-responsive chemiluminescent substrate (CPPO), and soybean oil as a retarder within F-127 micelles. This design enables a persistent chemically initiated electron exchange luminescence (CIEEL) process upon H2O2 encounter, producing intense NIR chemiluminescence and sustained 1O2 production without external irradiation. This platform not only achieves highly sensitive and specific imaging of H2O2-associated diseases but also facilitates self-luminescent photodynamic therapy, offering a promising external light excitation-free theranostic strategy for clinical translation.
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Junhao Huang, Lin Yang, Yufeng Xiao, Yuxi Li, Jiachang Huang, Ben Zhong Tang, Benzhao He (2026). A H2O2-triggered NIR chemiluminescence nanoprobe with aggregation-induced emission properties for in vivo inflammation imaging and tumor theranostics. SCIENCE CHINA Materials. https://doi.org/10.1007/s40843-026-4117-y
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Frequently Asked Questions
What is the mechanism of chemiluminescence generation in CPPO@TN NPs, and how does it sustain 1O2 production without external light?
The nanoprobe utilizes CPPO, a chemiluminescent substrate that reacts with H2O2 to generate high-energy intermediates via a chemically initiated electron exchange luminescence (CIEEL) process. This energy is transferred to the AIE photosensitizer TN, which emits NIR light and produces singlet oxygen (1O2) through energy transfer. The soybean oil acts as a retarder, slowing the reaction to prolong the luminescence and 1O2 generation, enabling sustained therapeutic effects without external irradiation.
How does the nanoprobe achieve high signal-to-noise ratio in in vivo imaging, and what are the specific performance metrics?
The nanoprobe emits in the NIR region, which minimizes tissue autofluorescence and enhances tissue penetration. In murine models of drug-induced liver injury and peritonitis, the nanoprobe demonstrated highly sensitive and specific imaging with exceptional signal-to-noise ratios, as evidenced by clear delineation of inflamed tissues. The absence of external excitation eliminates background autofluorescence, further improving the signal-to-background ratio.
What is the therapeutic efficacy of CPPO@TN NPs in tumor models, and how does it compare to conventional photodynamic therapy?
In a 4T1 tumor-bearing mouse model, CPPO@TN NPs significantly inhibited tumor growth through self-luminescent photodynamic therapy. The sustained 1O2 production, driven by the CIEEL process, induced effective cytotoxicity in cancer cells. Unlike conventional photodynamic therapy requiring external light, this system operates autonomously, overcoming limitations of light penetration and enabling treatment of deep-seated tumors.
What are the potential clinical applications of this nanoprobe beyond inflammation imaging and tumor theranostics?
Given its H2O2-triggered activation and NIR chemiluminescence, the nanoprobe could be adapted for imaging and therapy of other H2O2-associated diseases, such as neurodegenerative disorders, cardiovascular diseases, and diabetic complications. Its modular design allows for tuning the AIE photosensitizer and chemiluminescent substrate to target specific biomarkers, broadening its diagnostic and therapeutic utility.
What are the limitations of the current nanoprobe design, and what improvements are needed for clinical translation?
The current nanoprobe relies on endogenous H2O2 levels, which may be insufficient in some pathological contexts. Future work could incorporate amplification strategies or targeting ligands to enhance specificity and sensitivity. Additionally, long-term biocompatibility, biodistribution, and clearance profiles need thorough evaluation in preclinical models to ensure safety and efficacy for clinical use.
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