Hu Yaqin, Cheng Long, Guo Xun, Zheng Min, Zhang Wei, Wang Xingyue, Tang Rui, Chen Qiaoqi, Guo Yuan, Cao Yang, Wang Zhigang, Ran Haitao
Department of Ultrasound, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People's Republic of China.
Chongqing Key Laboratory of Ultrasound Molecular Imaging and Therapy, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People's Republic of China.
Biomater Res. 2025 May 15;29:0207. doi: 10.34133/bmr.0207. eCollection 2025.
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.
三阴性乳腺癌（TNBC）是一种具有高度侵袭性的癌症，其较差的治疗结果通常与肿瘤微环境的机械特性有关，该微环境的特征是细胞外基质（ECM）柔韧性改变和硬度增加。在此，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），用于精确调节ECM的硬度，以对TNBC进行机械免疫治疗。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，其损害肿瘤细胞并重塑ECM的硬度。同时，软化的ECM可使肿瘤血管正常化，以缓解缺氧并增加活性氧的产生，从而提高声动力疗法的疗效并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。总体而言，本研究提供了一种独特的“声-气介导的机械免疫”策略来调节ECM，有可能克服当前TNBC治疗的局限性。
