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A NIR-II Photoacoustic Probe for High Spatial Quantitative Imaging of Tumor Nitric Oxide in Vivo
Zhiyong Jiang1,2, Changli Zhang3, Qian Sun2
1College of Materials Science and Engineering, Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing, 210037, China.
Abstract:
Nitric oxide (NO) exhibits both pro- and anti-tumor effects. Therefore, real-time in vivo imaging and quantification of tumor NO dynamics are essential for understanding the conflicting roles of NO played in pathophysiology. The current molecular probes, however, cannot provide high-resolution imaging in deep tissues, making them unsuitable for these purposes. Herein, we designed a photoacoustic probe with an absorption maximum beyond 1000 nm for high spatial quantitative imaging of in vivo tumor NO dynamics. The probe exhibits remarkable sensitivity, selective ratiometric response behavior, and good tumor-targeting abilities, facilitating ratiometric imaging of tumor NO throughout tumor progression in a micron-resolution level. Using the probe as the imaging agent, we successfully quantified NO dynamics in tumor, liver and kidney. We have pinpointed an essential concentration threshold of around 80 nmol/cm3 for NO, which plays a crucial role in the "double-edged-sword" function of NO in tumors. Furthermore, we revealed a reciprocal relationship between the NO concentration in tumors and that in the liver, providing initial insights into the possible NO-mediated communication between tumor and the liver. We believe that the probe will help resolve conflicting aspects of NO biology and guide the design of imaging agents for tumor diagnosis and anti-cancer drug screening.
Insights
This study introduces a novel photoacoustic probe for high-resolution imaging of nitric oxide (NO) in tumors. The probe reveals a critical NO concentration threshold influencing its dual role in cancer and suggests liver-tumor communication.
Area of Science:
- Biomedical Engineering
- Molecular Imaging
- Cancer Research
Background:
- Nitric oxide (NO) has complex roles in tumor development, acting as both a promoter and inhibitor.
- Accurate in vivo imaging and quantification of tumor NO dynamics are crucial for understanding its pathophysiology.
- Existing molecular probes lack the resolution for deep tissue imaging of NO.
Purpose of the Study:
- To develop a photoacoustic probe for high-resolution, quantitative imaging of in vivo tumor nitric oxide (NO) dynamics.
- To investigate the role of NO concentration thresholds in the dual function of NO in tumors.
- To explore potential NO-mediated communication between tumors and other organs like the liver.
Main Methods:
- Design and synthesis of a near-infrared photoacoustic probe (>1000 nm absorption) for NO detection.
- In vivo ratiometric imaging of tumor NO dynamics with micron-resolution.
- Quantification of NO levels in tumors, liver, and kidneys.
Main Results:
- The developed probe demonstrated high sensitivity, selectivity, and tumor-targeting capabilities.
- A critical NO concentration threshold of approximately 80 nmol/cm³ was identified, crucial for NO's "double-edged-sword" effect in tumors.
- A reciprocal relationship between NO concentrations in tumors and the liver was observed.
Conclusions:
- The novel photoacoustic probe enables high-resolution spatiotemporal imaging and quantification of tumor NO dynamics.
- The findings elucidate the critical concentration threshold for NO's pro- and anti-tumor effects.
- This work provides insights into inter-organ NO communication and aids in designing new imaging agents for cancer diagnosis and drug screening.
