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Theranostics 2020; 10(8):3430-3450. doi:10.7150/thno.38422 This issue Cite

Research Paper

Smart Sorting of Tumor Phenotype with Versatile Fluorescent Ag Nanoclusters by Sensing Specific Reactive Oxygen Species

Xin Chen^1,5*, Tiegong Wang^2*, Wenjun Le¹, Xin Huang¹, Minghui Gao¹, Qian Chen¹, Shuogui Xu³, Detao Yin⁵, Qingge Fu^3✉, Chengwei Shao^2✉, Bingdi Chen^1✉, Donglu Shi⁴

1. The Institute for Translational Nanomedicine, Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai, China.
2. Radiology Department of Changhai Hospital, The Second Military Medical University, Shanghai, China.
3. Department of Emergency, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
4. The Materials Science and Engineering Program, Dept. of Mechanical and Materials Engineering, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, Ohio, 45221, USA.
5. Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
* These authors contributed equally

✉ Corresponding authors: Q.F. (email: fqg7821com), C.S. (email: cwshaocom) or B.C. (email: inanochenedu.cn)

Abstract

Reactive oxygen species (ROS) play a crucial role in cancer formation and development, especially cancer metastasis. However, lack of a precise tool, which could accurately distinguish specific types of ROS, restricts an in-depth study of ROS in cancer development and progression. Herein, we designed smart and versatile fluorescent Ag nanoclusters (AgNCs) for sensitive and selective detection of different species of ROS in cells and tissues.

Methods: Firstly, dual-emission fluorescent AgNCs was synthesized by using bovine serum albumin (BSA) to sense different types of ROS (H₂O₂, O2•-, •OH). The responsiveness of the AgNCs to different species of ROS was explored by fluorescence spectrum, hydrodynamic diameter, and so on. Furthermore, dual-emission fluorescent AgNCs was used to sense ROS in tumor with different degrees of differentiation. Finally, the relationship between specific types of ROS and tumor cell invasion was explored by cell migration ability and the expression of cell adhesion and EMT markers.

Results: This dual-emission fluorescent AgNCs possessed an excellent ability to sensitively and selectively distinguish highly reactive oxygen species (hROS, including O₂•^-and •OH) from moderate reactive oxygen species (the form of H₂O₂), and exhibited no fluoresence and green fluorescence, respectively. The emission of AgNCs is effective in detecting cellular and tissular ROS. When cultured with AgNCs, malignant tumor cells exhibit non-fluorescence, while the benign tumor emits green and reduced red light and the normal cells appear in weak green and bright red fluorescence. We further verified that not just H₂O₂ but specific species of ROS (O₂•^-and •OH) were involved in cell invasion and malignant transformation. Our study warrants further research on the role of ROS in physiological and pathophysiological processes.

Conclusion: Taken together, AgNCs would be a promising approach for sensing ROS, and offer an intelligent tool to detect different kinds of ROS in tumors.

Keywords: Ag Nanoclusters, ROS, Tumor Phenotype

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