Electron transfer-triggered imaging of EGFR signaling activity

Jie Tan,Zhijun Sun,Weihong Tan,Chenxuan Zhao,Cailing Ji,Quan Yuan,Liming Tang,Caixin Zhang,Hao Li,Lei Zhang

doi:10.1038/s41467-022-28213-y

Jie Tan, Zhijun Sun + Show 8 more

Open Access

https://doi.org/10.1038/s41467-022-28213-y

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Abstract

In vivo electron transfer processes are closely related to the activation of signaling pathways, and, thus, affect various life processes. Indeed, the signaling pathway activation of key molecules may be associated with certain diseases. For example, epidermal growth factor receptor (EGFR) activation is related to the occurrence and development of tumors. Hence, monitoring the activation of EGFR-related signaling pathways can help reveal the progression of tumor development. However, it is challenging for current detection methods to monitor the activation of specific signaling pathways in complex biochemical reactions. Here we designed a highly sensitive and specific nanoprobe that enables in vivo imaging of electronic transfer over a broad range of spatial and temporal scales. By using the ferrocene-DNA polymer “wire”, the electrons transferred in a biochemical reaction can flow to persistent luminescent nanoparticles and change their electron distribution, thereby altering the optical signal of the particles. This electron transfer-triggered imaging probe enables mapping the activation of EGFR-related signaling pathways in a temporally and spatially precise manner. By offering precise visualization of signaling activity, this approach may offer a general platform not only for understanding molecular mechanisms in various biological processes but also for promoting disease therapies and drug evaluation.

Highlights

In vivo electron transfer processes are closely related to the activation of signaling pathways, and, affect various life processes
When ligands of the target molecules are present, the electron can transfer from the ligand to the persistent luminescence nanoparticle through the ferrocene-DNA polymer chain, leading to a change of afterglow signal (Fig. 1b)
The in vivo imaging of electron transfer in epidermal growth factor receptor (EGFR) signaling pathways was assessed in a mouse with lung cancer

Summary

Introduction

In vivo electron transfer processes are closely related to the activation of signaling pathways, and, affect various life processes. By using the ferrocene-DNA polymer “wire”, the electrons transferred in a biochemical reaction can flow to persistent luminescent nanoparticles and change their electron distribution, thereby altering the optical signal of the particles This electron transfer-triggered imaging probe enables mapping the activation of EGFR-related signaling pathways in a temporally and spatially precise manner. If the monitoring of tumor proliferation-associated signal pathway activity could be achieved, it would be possible to evaluate therapeutic behavior on this basis This possibility has motivated the need for developing novel strategies to implement in vivo monitoring of electron transfer processes that occur in signaling pathways. Since there are diverse signaling pathways in life activities, this electron transfer-triggered imaging approach provides a general platform, for understanding molecular mechanisms in various biological processes and for promoting disease therapies and drug evaluation

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