In vivo three-dimensional multispectral photoacoustic imaging of dual enzyme-driven cyclic cascade reaction for tumor catalytic therapy

Shan Lei,Nicholas Thomas Blum,Jing Lin,Meng Li,Feng Zhao,Weimin Yin,Dong-Yang Zhang,Jing Zhang,Peng Huang

doi:10.1038/s41467-022-29082-1

Abstract

Non-invasive visualization of dynamic molecular events in real-time via molecular imaging may enable the monitoring of cascade catalytic reactions in living systems, however effective imaging modalities and a robust catalytic reaction system are lacking. Here we utilize three-dimensional (3D) multispectral photoacoustic (PA) molecular imaging to monitor in vivo cascade catalytic therapy based on a dual enzyme-driven cyclic reaction platform. The system consists of a two-dimensional (2D) Pd-based nanozyme conjugated with glucose oxidase (GOx). The combination of nanozyme and GOx can induce the PA signal variation of endogenous molecules. Combined with the PA response of the nanozyme, we can simultaneously map the 3D PA signals of dynamic endogenous and exogenous molecules associated with the catalytic process, thus providing a real-time non-invasive visualization. We can also treat tumors under the navigation of the PA imaging. Therefore, our study demonstrates the imaging-guided potential of 3D multispectral PA imaging in feedback-looped cascade catalytic therapy.

Highlights

Non-invasive visualization of dynamic molecular events in real-time via molecular imaging may enable the monitoring of cascade catalytic reactions in living systems, effective imaging modalities and a robust catalytic reaction system are lacking
The PdMo bimetallene nanosheet (PMNS) was dominated by sheet-like morphology with an average diameter of 56 nm and well characterized by transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), powder X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) (Supplementary Figs. 1– 4 and Fig. 2a)
Lung Kinedy Tumor at 24 h post-injection (Fig. 4f, g and Supplementary Fig. 30). These results revealed that the partial PMNSG oxyHb and PMNSG (or PMNS) accumulated in liver, followed by another organs, which were consistent with the results obtained via inductively coupled plasma massspectrometry (ICP-MS) (Supplementary Fig. 31)

Summary

Introduction

Non-invasive visualization of dynamic molecular events in real-time via molecular imaging may enable the monitoring of cascade catalytic reactions in living systems, effective imaging modalities and a robust catalytic reaction system are lacking. Combined with the PA response of the nanozyme, we can simultaneously map the 3D PA signals of dynamic endogenous and exogenous molecules associated with the catalytic process, providing a real-time non-invasive visualization. During the pathological processes of cascade catalytic therapy, if the exogenous nanozymes break the current states of endogenous molecules, which can undergo an intrinsic signal evolution, providing a correlation between nanozyme states and the occurrence of molecular events in real-time. To achieve this goal, we need to develop a simple and robust nanozymebased cascade catalytic system. Two enzymes are used to construct a biodegradable cyclic cascade catalytic system (denoted as PMNSG)

Methods

Results

Conclusion