Journal
NANO RESEARCH
Volume 14, Issue 1, Pages 212-221Publisher
TSINGHUA UNIV PRESS
DOI: 10.1007/s12274-020-3070-8
Keywords
two-dimensional nanosheets; biodegradable; sonodynamic therapy; regulate immunosuppressive TME; immunotherapy
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Funding
- National Research Programs of China [2016YFA0201200]
- National Natural Science Foundation of China [91959104, 21927803, 51903182, 51525203]
- Natural Science Foundation of Jiangsu Province [BK20190826]
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- 111 Program from the Ministry of Education of China
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Zn-TCPP 2D nanosheets exhibit enhanced ROS generation for noninvasive SDT and have high loading capacity for oligodeoxynucleotides useful in activating immune responses.
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.
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