Yu Chenghao, Chen Desheng, Zhu Dingcheng, Feng Lili, Yang Lu, Berdimurodov Elyor, Zang Pengyu, Zhu Yanlin, Hu Yaoyu, Sang Jiaxu, Yang Piaoping
Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, P. R. China.
Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, P. R. China.
Adv Mater. 2025 Aug;37(33):e2501642. doi: 10.1002/adma.202501642. Epub 2025 May 30.
Extracellular matrix (ECM), a core member of tumor microenvironment, is ≈1.5-fold harder than the surrounding normal tissues. Regulating the stiffness of ECM can significantly impact physiological activities of tumor cells, such as growth, differentiation, and migration. Herein, a sonopiezoelectric-response nanoplatform consisting of CuBiS nanospheres (CBS NSs) is constructed for ECM remodeling. Sonopiezoelectric therapy (SPT) and chemodynamic therapy (CDT) are conducted using ultrasound (US) and near-infrared irradiation. Under US irradiation, the mechanical strain of CBS NSs causes piezoelectric polarization and promotes a redox reaction through energy band bending. The built-in electric field generated by US irradiation amplifies the efficiency of the Fenton-like reaction and substantially enhances reactive oxygen species production. Moreover, piezoelectric property-mediated electrical signals can allow Ca influx, upregulating the levels of matrix metalloproteinase (MMP)-2 and MMP-9. Integrating US irradiation with near-infrared irradiation generates localized heat, which can effectively denature tumor collagen, reduce tumor stiffness, and enhance the permeability of CBS NSs into solid tumors, thus improving the SPT effect. The combination of MMP upregulation and collagen degradation can maximize the benefits of ECM remodeling and synergistically enhance the cancer therapeutic efficacy of SPT/CDT. This SPT/CDT synergistic therapy and ECM remodeling platform is an innovative strategy for cancer therapy.
细胞外基质（ECM）是肿瘤微环境的核心组成部分，其硬度比周围正常组织约高1.5倍。调节ECM的硬度可显著影响肿瘤细胞的生理活动，如生长、分化和迁移。在此，构建了一种由CuBiS纳米球（CBS NSs）组成的声压电响应纳米平台用于ECM重塑。使用超声（US）和近红外照射进行声压电疗法（SPT）和化学动力疗法（CDT）。在US照射下，CBS NSs的机械应变导致压电极化，并通过能带弯曲促进氧化还原反应。US照射产生的内建电场放大了类芬顿反应的效率，并大幅提高活性氧的产生。此外，压电性质介导的电信号可使Ca内流，上调基质金属蛋白酶（MMP）-2和MMP-9的水平。将US照射与近红外照射相结合可产生局部热，其可有效使肿瘤胶原蛋白变性，降低肿瘤硬度，并增强CBS NSs进入实体瘤的渗透性，从而提高SPT效果。MMP上调与胶原蛋白降解的联合作用可最大化ECM重塑的益处，并协同增强SPT/CDT的癌症治疗效果。这种SPT/CDT协同疗法和ECM重塑平台是一种创新的癌症治疗策略。
