Yaqin Hu, Long Cheng, Xun Guo, Min Zheng, Wei Zhang, Xingyue Wang, Rui Tang, Qiaoqi Chen, Yuan Guo, Yang Cao, Zhigang Wang, Haitao Ran
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引用次数: 0
摘要
三阴性乳腺癌(TNBC)是一种高度侵袭性的癌症,其不良的治疗效果往往与肿瘤微环境的力学特性有关,其特征是细胞外基质(ECM)柔韧性改变和刚度增加。本文设计了一种机械免疫调节剂,即红细胞膜- ir780 - l -精氨酸纳米颗粒(R-I-LA NPs),以精确调节ECM的刚度,用于TNBC的机械免疫治疗。在肿瘤细胞中,低强度聚焦超声激活R-I-LA NPs产生活性氮物质,破坏肿瘤细胞,重塑ECM刚度。同时,软化后的ECM能使肿瘤血管正常化,缓解缺氧,增加活性氧的产生,从而提高声动力治疗的效果,刺激免疫原性细胞死亡。此外,R-I-LA NPs刺激免疫系统并抑制肺转移。总的来说,这项研究为ECM调节提供了一种独特的“声纳-气体介导的机械免疫”策略,有可能克服目前TNBC治疗的局限性。
Sono-Gas-Mediated Precise Stiffness Remodeling for Triple-Negative Breast Cancer Mechanical Immunotherapy.
Triple-negative breast cancer (TNBC) is a highly invasive cancer, and its poor therapeutic outcomes are often associated with the mechanical properties of the tumor microenvironment, which is characterized by altered extracellular matrix (ECM) flexibility and increased stiffness. Herein, a mechanical immunomodulator, namely, red blood cell membrane-IR780-L-arginine nanoparticles (R-I-LA NPs), was designed to precisely regulate the stiffness of the ECM for mechanical immunotherapy of TNBC. In tumor cells, the low-intensity focused ultrasound activates R-I-LA NPs to produce reactive nitrogen species, which damages tumor cells and remodels the stiffness of ECM. Meanwhile, the softened ECM can normalize the tumor vasculature to alleviate hypoxia and increase the production of reactive oxygen species, thereby enhancing the efficacy of sonodynamic therapy and stimulating immunogenic cell death. Additionally, R-I-LA NPs stimulate the immune system and suppress pulmonary metastasis. Overall, this study offers a distinctive "sono-gas-mediated mechanical immunity" strategy for ECM regulation, potentially overcoming current TNBC therapy limitations.