A highly potent ruthenium(II)-sonosensitizer and sonocatalyst for in vivo sonotherapy

Chao Liang,Shuangling Luo,Qianling Zhang,Can Huang,Pingyu Zhang,Huaiyi Huang,Jiaen Xie

doi:10.1038/s41467-021-25303-1

Chao Liang, Shuangling Luo + Show 5 more

Open Access

https://doi.org/10.1038/s41467-021-25303-1

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Abstract

As a basic structure of most polypyridinal metal complexes, [Ru(bpy)3]2+, has the advantages of simple structure, facile synthesis and high yield, which has great potential for scientific research and application. However, sonodynamic therapy (SDT) performance of [Ru(bpy)3]2+ has not been investigated so far. SDT can overcome the tissue-penetration and phototoxicity problems compared to photodynamic therapy. Here, we report that [Ru(bpy)3]2+ is a highly potent sonosensitizer and sonocatalyst for sonotherapy in vitro and in vivo. [Ru(bpy)3]2+ can produce singlet oxygen (1O2) and sono-oxidize endogenous 1,4-dihydronicotinamide adenine dinucleotide (NADH) under ultrasound (US) stimulation in cancer cells. Furthermore, [Ru(bpy)3]2+ enables effective destruction of mice tumors, and the therapeutic effect can reach deep tissues over 10 cm under US irradiation. This work paves a way for polypyridinal metal complexes to be applied to the noninvasive precise sonotherapy of cancer.

Highlights

As a basic structure of most polypyridinal metal complexes, [Ru(bpy)3]2+, has the advantages of simple structure, facile synthesis and high yield, which has great potential for scientific research and application
Metal-based photosensitizers were widely applied for photodynamic therapy (PDT), owing to their high photostability and 1O2 generation[5,6,7,8,9,10,11,12,13]
Sonodynamic therapy (SDT) is a non-invasive therapeutic strategy, which is triggered by the high tissue penetration ultrasound[18,19,20,21]

Summary

Introduction

As a basic structure of most polypyridinal metal complexes, [Ru(bpy)3]2+, has the advantages of simple structure, facile synthesis and high yield, which has great potential for scientific research and application. SDT can overcome the tissue-penetration and phototoxicity problems compared to photodynamic therapy. Metal-based photosensitizers were widely applied for photodynamic therapy (PDT), owing to their high photostability and 1O2 generation[5,6,7,8,9,10,11,12,13]. Sonodynamic therapy (SDT) is a non-invasive therapeutic strategy, which is triggered by the high tissue penetration ultrasound (up to 10 cm)[18,19,20,21]. Organic sonosensitizers often exhibit limited stability under US irradiation[28,29,30], and some of complicated nanoparticles show low ROS quantum yield decreasing SDT efficiency[31]. NADH is related to the preservation of the redox balance within cells as well as prevents ROS related cell damages

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