二维 Ti3C2 纳米片上原位生长的纳米晶体 TiO2 通过光声动力学治疗和免疫学具有抗肿瘤活性。
In-Situ Grown Nanocrystal TiO2 on 2D Ti3C2 Nanosheets with Anti-Tumor Activity from Photo-Sonodynamic Treatment and Immunology.
发表日期：2024
作者：
Hailing Yu, Yongquan Huang, Zhisheng Nong, Xi Lin, Kexin Tang, Zeyu Cai, Kaichen Huang, Ting Yu, Huimin Lan, Qianqian Zhang, Qiang Wang, Lei Yang, Jingchuan Zhu, Lili Wu, Hui Luo
来源：
International Journal of Nanomedicine
摘要：
传统的癌症治疗策略往往毒副作用严重且治疗效果不佳。为了解决与克服肿瘤复杂性相关的长期存在的问题，我们开发了一种基于2D Ti3C2结构原位氧化的新型纳米酶，对肿瘤进行同步光疗和声动力治疗。 Ti3C2纳米酶表现出多酶活性，包括内在过氧化物酶（POD）活性，可与肿瘤微环境中的H2O2发生反应。这种新材料可以在体内构建Ti3C2/TiO2异质结构，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，这种纳米酶会发生抗癌免疫反应。体内实验表明Ti3C2/TiO2异质结构抑制肿瘤生长。补充地，我们的结果表明Ti3C2/TiO2异质结构通过招募细胞毒性T细胞增强肿瘤的免疫原性活性，从而增强肿瘤消融效果。机制研究一致表明，活性氧 (ROS) 在体外和体内通过调节 NRF2/OSGIN1 信号传导来调节 HCC 细胞的凋亡。因此，Ti3C2纳米酶通过其协同调节ROS和增强肿瘤微环境中细胞毒性T细胞的免疫浸润的能力，有效抑制肿瘤。这些发现为增强2D Ti3C2纳米片开辟了新途径，并提出了开发更有效的声敏剂的新方法用于治疗癌症。© 2024 Yu et al.
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 Ti3C2 structure to perform simultaneous phototherapy and sonodynamic therapy on tumors. Ti3C2 nanozymes exhibit multi-enzyme activity, including intrinsic peroxidase (POD) activities, which can react with H2O2 in the tumor microenvironment. This new material can construct Ti3C2/TiO2 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 Ti3C2/TiO2 heterostructure inhibited tumor growth.Complementarily, our results showed that the Ti3C2/TiO2 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, Ti3C2 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 Ti3C2 nanosheets and suggest a new way to develop more effective sonosensitizers for the treatment of cancer.© 2024 Yu et al.