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Nano Research

Article Title

Sonodynamic therapy with immune modulatable two-dimensional coordination nanosheets for enhanced anti-tumor immunotherapy

Authors

Wenjun Zhu, Institute of Functional Nano & Soft Materials , Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou 215123, China
Qian Chen, Institute of Functional Nano & Soft Materials , Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou 215123, China
Qiutong Jin, Institute of Functional Nano & Soft Materials , Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou 215123, China
Yu Chao, Institute of Functional Nano & Soft Materials , Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou 215123, China
Lele Sun, Institute of Functional Nano & Soft Materials , Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou 215123, China
Xiao Han, Institute of Functional Nano & Soft Materials , Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou 215123, China
Jun Xu, Institute of Functional Nano & Soft Materials , Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou 215123, China
Longlong Tian, Institute of Functional Nano & Soft Materials , Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou 215123, China
Jinglei Zhang, Institute of Functional Nano & Soft Materials , Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou 215123, China
Teng Liu, State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences , Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
Zhuang Liu, Institute of Functional Nano & Soft Materials , Collaborative Innovation Center of Suzhou Nano Science and Technology, Jiangsu Key Laboratory for Carbon-based Functional Materials and Devices, Soochow University, Suzhou 215123, China

Keywords

two-dimensional nanosheets, biodegradable, sonodynamic therapy, regulate immunosuppressive TME, immunotherapy

Abstract

Ultrasound with deep penetration depth and high security could be adopted in sonodynamic therapy (SDT) by activating sonosensitizers to generate cytotoxic reactive oxygen species (ROS). Herein, two-dimensional (2D) coordination nanosheets composed of Zn2+ and Tetrakis(4-carboxyphenyl) porphyrin (TCPP) are fabricated. While exhibiting greatly enhanced ultrasound-triggered ROS generation useful for noninvasive SDT, such Zn-TCPP 2D nanosheets show high loading capacity of oligodeoxynucleotides such as cytosine-phosphorothioate-guanine (CpG), which is a potent toll like receptor 9 (TLR9) agonist useful in activating immune responses. Highly effective SDT of primary tumors could release tumor-associated antigens, which working together with Zn-TCPP/CpG adjuvant nanosheets could function like whole-tumor-cell vaccines and trigger tumor-specific immune responses. Interestingly, ultrasound itself could strengthen anti-tumor immune responses by improving the tumor-infiltration of T cells and limiting regulatory T cells in the tumor microenvironment. Thus, SDT using Zn-TCPP/CpG nanosheets after destruction of primary tumors could induce potent antitumor immune responses to inhibit distant abscopal tumors without direct SDT treatment. Moreover, SDT with Zn-TCPP/CpG could trigger strong immunological memory effects to inhibit cancer recurrence after elimination of primary tumors. Therefore, the 2D coordination nanosheet may be a promising platform to deliver potent SDT-triggered immunotherapy for highly effective cancer treatment.

Publisher

Tsinghua University Press

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