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

• Published in: Nano research 2021, Vol.14 (1), p.212-221
• Main Authors: Zhu, Wenjun, Chen, Qian, Jin, Qiutong, Chao, Yu, Sun, Lele, Han, Xiao, Xu, Jun, Tian, Longlong, Zhang, Jinglei, Liu, Teng, Liu, Zhuang
• Format: Article
• Language: English
• Subjects: Antigen (tumor-associated); Antigens; Antitumor activity; Atomic/Molecular Structure and Spectra; Biomedicine; Biotechnology; Cancer; Chemistry and Materials Science; Condensed Matter Physics; Coordination; CpG islands; Cytosine; Cytotoxicity; Guanine; Immune system; Immunological memory; Immunology; Immunoregulation; Immunotherapy; Lymphocytes; Lymphocytes T; Materials Science; Metastases; Nanosheets; Nanotechnology; Oligonucleotides; Penetration depth; Phosphorothioate; Porphyrins; Proteins; Reactive oxygen species; Research Article; TLR9 protein; Toll-like receptors; Tumors; Ultrasonic imaging; Ultrasound; Zinc
• ISSN: 1998-0124; 1998-0000
• DOI: 10.1007/s12274-020-3070-8

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 Zn 2+ 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.