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.

通过激活声敏剂产生细胞毒性的活性氧（ROS），可以在声动力学治疗（SDT）中采用具有深穿透深度和高安全性的超声。本文中，由Zn ²⁺组成的二维（2D）配位纳米片制备了四（4-羧基苯基）卟啉（TCPP）。此类Zn-TCPP 2D纳米片虽然表现出大大增强的超声触发ROS生成能力，可用于无创SDT，但仍表现出高脱氧核苷酸（如胞嘧啶-硫代磷酸酯-鸟嘌呤（CpG））的高负载能力，这是一种有效的收费受体9（TLR9）激动剂激活免疫反应。原发性肿瘤的高效SDT可以释放与肿瘤相关的抗原，该抗原与Zn-TCPP / CpG佐剂纳米片协同工作，可以像全肿瘤细胞疫苗一样起作用，并触发肿瘤特异性免疫反应。有趣的是，超声本身可以通过改善T细胞的肿瘤浸润和限制肿瘤微环境中的调节性T细胞来增强抗肿瘤免疫反应。从而，原发性肿瘤破坏后使用Zn-TCPP / CpG纳米片的SDT无需直接SDT治疗即可诱导有效的抗肿瘤免疫反应，从而抑制远处的远隔肿瘤。此外，具有Zn-TCPP / CpG的SDT可以触发强大的免疫记忆效应，从而抑制原发肿瘤消除后的癌症复发。因此，二维配位纳米片可能是一个有前途的平台，可为有效的癌症治疗提供有效的SDT触发的免疫疗法。