Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong, People's Republic of China.
Department of Ultrasound, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, People's Republic of China.
Int J Nanomedicine. 2024 Aug 6;19:7963-7981. doi: 10.2147/IJN.S457112. eCollection 2024.
Traditional cancer treatment strategies often have severe toxic side effects and poor therapeutic efficacy. To address the long-standing problems related to overcoming the complexity of tumors, we develop a novel nanozyme based on the in situ oxidation of 2D TiC structure to perform simultaneous phototherapy and sonodynamic therapy on tumors. TiC nanozymes exhibit multi-enzyme activity, including intrinsic peroxidase (POD) activities, which can react with HO in the tumor microenvironment. This new material can construct TiC/TiO heterostructures in vivo.
Photothermal (PTT), sonodynamic (SDT) effects, and photoacoustic (PA) image-guided synergy therapy can be achieved. Finally, anticancer immune responses occur with this nanozyme. In vivo experiments revealed that the TiC/TiO heterostructure inhibited tumor growth.
Complementarily, our results showed that the TiC/TiO heterostructure enhanced the immunogenic activity of tumors by recruiting cytotoxic T cells, thereby enhancing the tumor ablation effect. Mechanistic studies consistently indicated that Reactive Oxygen Species (ROS) regulates apoptosis of HCC cells by modulating NRF2/OSGIN1 signaling both in vitro and in vivo. As a result, TiC nanozyme effectively inhibited tumor through its synergistic ability to modulate ROS and enhance immune infiltration of cytotoxic T cells in the tumor microenvironment.
These findings open up new avenues for enhancing 2D TiC nanosheets and suggest a new way to develop more effective sonosensitizers for the treatment of cancer.
传统的癌症治疗策略往往具有严重的毒副作用和较差的治疗效果。为了解决与克服肿瘤复杂性相关的长期问题，我们开发了一种基于二维 TiC 结构原位氧化的新型纳米酶，以对肿瘤进行同时光疗和超声动力治疗。TiC 纳米酶具有多种酶活性，包括内在过氧化物酶（POD）活性，可与肿瘤微环境中的 HO 反应。这种新材料可以在体内构建 TiC/TiO 异质结构。
可以实现光热（PTT）、声动力（SDT）效应和光声（PA）图像引导协同治疗。最后，该纳米酶会引发抗癌免疫反应。体内实验表明，TiC/TiO 异质结构通过募集细胞毒性 T 细胞抑制肿瘤生长。
此外，我们的结果表明，TiC/TiO 异质结构通过调节 NRF2/OSGIN1 信号通路增强了肿瘤的免疫原性活性，从而增强了肿瘤消融效果。机制研究一致表明，活性氧（ROS）通过调节 NRF2/OSGIN1 信号通路在体外和体内调节 HCC 细胞凋亡。结果，TiC 纳米酶通过其调节 ROS 和增强肿瘤微环境中细胞毒性 T 细胞免疫浸润的协同能力有效抑制了肿瘤。
这些发现为增强二维 TiC 纳米片开辟了新途径，并为开发更有效的声敏剂治疗癌症提供了新方法。
