Hypoxia-activated probe for NIR fluorescence and photoacoustic dual-mode tumor imaging

Meng Li,Huan Li,Qian Wu,Niu Niu,Jiachang Huang,Lingmin Zhang,Ying Li,Dong Wang,Ben Zhong Tang

doi:10.1016/j.isci.2021.102261

Abstract

SummaryConstruction of tumor microenvironment responsive probe with more than one imaging modality, in particular toward hypoxia of solid tumors, is an appealing yet significantly challenging task. In this work, we designed a hypoxia-activated probe TBTO (Triphenylamine-Benzothiadiazole-Triphenylamine derivative featuring four diethylamino N-Oxide groups) for in vivo imaging. TBTO could undergo bioreduction in a hypoxic microenvironment to yield compound TBT sharing both near-infrared (NIR) aggregation-induced emission and strong twisted intramolecular charge transfer features, which endows the probe with excellent performance in NIR fluorescence and photoacoustic dual-mode tumor imaging. This study offers useful insights into designing a new generation agent for clinical cancer diagnosis.

Highlights

It is generally accepted that the rapid proliferation of tumor cells and abnormal vasculature in solid tumors could result in an inadequate supply of oxygen and lead to a hypoxic microenvironment, which is strongly associated with tumor propagation, malignant progression, and treatment resistance (Brown and Wilson, 2004; Harris, 2002; Rankin et al, 2016)
TBTO could undergo bioreduction in a hypoxic microenvironment to yield compound TBT sharing both near-infrared (NIR) aggregation-induced emission and strong twisted intramolecular charge transfer features, which endows the probe with excellent performance in NIR fluorescence and photoacoustic dual-mode tumor imaging
Design and synthesis of TBT and TBTO The design of the hypoxia probe TBTO was based on previous reports demonstrating that the dimethylamino/diethylamino N-oxide group could be converted to dimethylamino/diethylamino group by reductases, such as cytochrome P450 (CYP450), over-produced in hypoxic regions of solid tumors (Albertella et al, 2008; Knox et al, 2017; Nishida et al, 2010)

Summary

Introduction

It is generally accepted that the rapid proliferation of tumor cells and abnormal vasculature in solid tumors could result in an inadequate supply of oxygen and lead to a hypoxic microenvironment, which is strongly associated with tumor propagation, malignant progression, and treatment resistance (Brown and Wilson, 2004; Harris, 2002; Rankin et al, 2016). The ultrasound signal is much less scattered in biological tissue than the optical signal, which enables high-resolution PA imaging even at centimeter depths (Liu et al, 2016; Mallidi et al, 2011). Despite these merits, activatable PA agents, which show PA signal only in the presence of specific stimuli, have rarely been reported for in vivo applications (Knox et al, 2017; Miao et al, 2016; Roberts et al, 2018)

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Discussion

Conclusion