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Diagnosing Orthotopic Lung Tumor Using a NTR-Activatable Near-Infrared Fluorescent Probe by Tracheal Inhalation
Jun Yan1, Kaizhen Wang1, Lijuan Gui1
1Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, 639 Longmian Road, Jiangning District, Nanjing 210009, China.
Abstract:
Nitroreductase (NTR) is an enzyme that is upregulated under tumor-depleted oxygen conditions. The majority of studies have been conducted on NTR, but many existing fluorescent imaging tools for monitoring NTR inevitably suffer from weak targeting, low sensitivity, and simple tumor models. Research on diagnosing lung tumors has been very popular in recent years, but targeting assays in orthotopic lung tumors is still of great research value, as such models better mimic the reality of cancer in the organism. Here, we developed a novel near-infrared (NIR) fluorescent probe IR-ABS that jointly targets NTR and carbonic anhydrase IX (CAIX). IR-ABS has excellent sensitivity and selectivity and shows exceptional NTR response in spectroscopic tests. The measurements ensured that this probe has good biosafety in both cells and mice. A better NTR response was found in hypoxic tumor cells at the cellular level, distinguishing tumor cells from normal cells. In vivo experiments demonstrated that IR-ABS achieves a hypoxic response at the zebrafish level and enables rapid and accurate tumor margin distinguishment in different mouse tumor models. More importantly, we successfully applied IR-ABS for NTR detection in orthotopic lung tumor models, further combined with tracheal inhalation drug delivery to improve targeting. To the best of our knowledge, we present for the first time a near-infrared imaging method for targeting lung cancerous tumor in situ via tracheal inhalation drug delivery, in contrast to the reported literature. This NIR fluorescence diagnostic strategy for targeting orthotopic lung cancer holds exciting potential for clinical aid in cancer diagnosis.
Insights
A new near-infrared fluorescent probe, IR-ABS, targets both nitroreductase (NTR) and carbonic anhydrase IX (CAIX). This probe offers sensitive and selective detection of hypoxic lung tumors, improving in vivo imaging and diagnosis.
Area of Science:
- Biomedical Imaging
- Molecular Imaging
- Cancer Diagnostics
Background:
- Nitroreductase (NTR) is upregulated in hypoxic tumors, making it a potential diagnostic target.
- Existing fluorescent imaging tools for NTR often lack sensitivity, selectivity, and effective tumor models.
- Orthotopic lung tumor models are crucial for realistic cancer research, but effective targeting assays are needed.
Purpose of the Study:
- To develop a novel near-infrared (NIR) fluorescent probe for enhanced tumor detection.
- To create a probe that targets both NTR and carbonic anhydrase IX (CAIX).
- To evaluate the probe's efficacy in various cancer models, including orthotopic lung tumors.
Main Methods:
- Development of a novel NIR fluorescent probe, IR-ABS.
- Spectroscopic testing for sensitivity and selectivity.
- In vitro testing in hypoxic tumor cells.
- In vivo testing in zebrafish and mouse tumor models.
- Application in orthotopic lung tumor models with tracheal inhalation drug delivery.
Main Results:
- IR-ABS demonstrated excellent sensitivity and selectivity with a strong NTR response.
- The probe showed good biosafety in cellular and animal studies.
- IR-ABS effectively distinguished hypoxic tumor cells from normal cells.
- In vivo experiments showed accurate tumor margin identification in mouse models.
- Successful application in orthotopic lung tumors using a novel drug delivery method.
Conclusions:
- IR-ABS is a highly sensitive and selective NIR fluorescent probe for detecting NTR and CAIX.
- The probe enables effective imaging of hypoxic tumors in various models, including orthotopic lung cancer.
- Tracheal inhalation drug delivery combined with IR-ABS offers a novel strategy for in situ lung cancer diagnosis.
- This NIR fluorescence diagnostic strategy shows significant potential for clinical applications in lung cancer detection.
