# Dual-locked strategy for fluorescence/chemiluminescence dual-modal imaging reprogramming

## TL;DR

A new dual-modal imaging probe allows sequential fluorescence and chemiluminescence imaging to detect carbon monoxide in a colitis model.

## Contribution

A novel 'FL-trigger-CL' dual-modal probe with a dual-locked strategy for time-controlled imaging is introduced.

## Key findings

- The FTC-01 probe successfully detected carbon monoxide in cells and a mouse colitis model.
- The dual-locked strategy enables on-demand activation of chemiluminescence after fluorescence detection.
- The probe platform shows compatibility for integrating additional sensing units.

## Abstract

Fluorescence (FL) and chemiluminescence (CL) each offer unique advantages for molecular imaging. FL allows for continuous and real-time tracking of analytes, while CL provides an ultra-high signal-to-background ratio by eliminating the need for exogenous excitation light. Integrating these two modalities for imaging presents significant synergies as well as challenges. However, the rarely reported FL/CL dual-modal probes are typically limited to a “CL–FL” mode, in which both FL and CL signals are activated simultaneously, with the transient CL signals being captured instantly and processed preferentially. In this study, we designed a novel near-infrared FL/CL dual-modal probe that introduces an innovative “FL-trigger-CL” mode for imaging. This approach employs a dual-locked strategy, allowing for flexible and time-controlled triggering of the CRET-based redshift CL signal dependent on fluoride-ion-mediated desilylation, a biocompatible bioorthogonal chemistry. The probe, named FTC-01, was successfully applied to detect carbon monoxide, an endogenous inflammatory biomarker, in both cells and mice with colitis, incorporating FL for primary detection and CL for accurate in-depth detection. This advancement is expected to enhance the application of this dual-modal imaging logic in disease diagnosis and drug candidate screening. Furthermore, our dual-locked probe platform demonstrates excellent compatibility and the potential for expansion, facilitating the integration of a broader range of sensing units and guiding the rational design of dual-modal probes in the future.

A dual-locked probe enables sequential “FL-trigger-CL” imaging, allowing on-demand activation of near-infrared chemiluminescence to validate carbon monoxide elevation in a live colitis model.