Facilitation of molecular motion to develop turn-on photoacoustic bioprobe for detecting nitric oxide in encephalitis

Ji Qi,Fei Xu,Xiaoyan Zhang,Xue Xue,Jacky W Y Lam,Yutong Zhou,Haoke Zhang,Ryan T K Kwok,Xingchen Duan,Zheng Zhao,Ben Zhong Tang,Liwen Huang,Dan Ding,Leyan Feng

doi:10.1038/s41467-021-21208-1

Abstract

Nitric oxide (NO) is an important signaling molecule overexpressed in many diseases, thus the development of NO-activatable probes is of vital significance for monitoring related diseases. However, sensitive photoacoustic (PA) probes for detecting NO-associated complicated diseases (e.g., encephalitis), have yet to be developed. Herein, we report a NO-activated PA probe for in vivo detection of encephalitis by tuning the molecular geometry and energy transformation processes. A strong donor-acceptor structure with increased conjugation can be obtained after NO treatment, along with the active intramolecular motion, significantly boosting “turn-on” near-infrared PA property. The molecular probe exhibits high specificity and sensitivity towards NO over interfering reactive species. The probe is capable of detecting and differentiating encephalitis in different severities with high spatiotemporal resolution. This work will inspire more insights into the development of high-performing activatable PA probes for advanced diagnosis by making full use of intramolecular motion and energy transformation processes.

Highlights

Nitric oxide (NO) is an important signaling molecule overexpressed in many diseases, the development of NO-activatable probes is of vital significance for monitoring related diseases
Active intramolecular motion can promote the release of excitation energy via nonradiative decay, a process which determines how much absorbed light can be converted to heat and is closely linked to several important biological techniques such as photoacoustic (PA) imaging[8,9]
The long aliphatic chains are designed to retain some flexible space between the conjugated backbones, which would be favourable for intramolecular motions in aggregate state (e.g., NPs)[8,45]

Summary

Introduction

Nitric oxide (NO) is an important signaling molecule overexpressed in many diseases, the development of NO-activatable probes is of vital significance for monitoring related diseases. Most molecular rotors are only active in solution, and exhibit limited intramolecular motion in aggregate forms such as NPs, which are more useful for biological applications[23,24,25] Another issue for current PA imaging is that most reported PA probes are in “always-on” state and lack specificity. PA signals from surrounding normal tissue frequently interfere with signal at the site of interest, leading to false diagnostic outcomes[26,27] One solution for this problem is the exploration of activatable PA contrast agents with “off-on” signal in response to a specific biomarker, which can substantially improve the SBR and real-time imaging capability in vivo[28,29,30]. It is challenging to develop highly specific and sensitive NO-activated PA nanoprobes to enable precise and in vivo diagnosis of NO-related disease in deep tissue, such as encephalitis

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Conclusion