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, No. 52 of Meihuadong Road, Xiangzhou District, Zhuhai, Guangdong 519099, China.
Department of Ultrasound, The Fifth Affiliated Hospital, Sun Yat-sen University, No. 52 of Meihuadong Road, Xiangzhou District, Zhuhai, Guangdong 519099, China.
ACS Appl Mater Interfaces. 2024 Feb 21;16(7):8275-8288. doi: 10.1021/acsami.3c14865. Epub 2024 Feb 9.
Tumor therapy presents significant challenges, and conventional treatments exhibit limited therapeutic effectiveness. Imbalance of calcium homeostasis as a key cause of tumor cell death has been extensively studied in tumor therapy. Calcium overload therapy has garnered significant interest as a new cancer treatment strategy. This study involves the synthesis of a transformable nanosonosensitizer with a shell of a calcium ion nanomodulator. The nanosystem is designed to induce mitochondrial dysfunction by combining the calcium ion nanomodulator, nanosonosensitizer, and chemotherapeutic drug. Under ultrasound-activated conditions, CaCO dissolves in the tumor microenvironment, causing the nanosonosensitizer to switch from the "off" to the "on" state of ROS generation, exacerbating mitochondrial calcium overload. A two-dimensional TiC/TiO heterostructure generates reactive oxygen species (ROS) under ultrasound and exhibits an efficient sonodynamic effect, enhancing calcium overload. Under ultrasound irradiation, TiC/TiO@CaCO/KAE causes multilevel damage to mitochondria by combining the effects of rapid Ca release, inhibiting Ca efflux, enhancing tumor inhibition, and converting a "cold" tumor into a "hot" tumor. Therefore, this study proposes a method to effectively combine mitochondrial Ca homeostasis and sonodynamic therapy (SDT) by the preparing pH-sensitive, double-activated, and multifunctional TiC/TiO-based nanosystems for cancer therapy.
肿瘤治疗存在重大挑战，传统治疗方法的疗效有限。钙稳态失衡是肿瘤细胞死亡的一个关键原因，在肿瘤治疗中已经得到了广泛的研究。钙超载治疗作为一种新的癌症治疗策略引起了广泛关注。本研究涉及合成一种具有钙离子纳米调节剂外壳的可变形纳米声敏剂。该纳米系统通过结合钙离子纳米调节剂、纳米声敏剂和化疗药物来诱导线粒体功能障碍。在超声激活条件下，CaCO 在肿瘤微环境中溶解，导致纳米声敏剂从 ROS 产生的“关闭”状态切换到“开启”状态，加剧线粒体钙超载。二维 TiC/TiO 异质结构在超声下产生活性氧（ROS），并表现出高效的声动力学效应，增强钙超载。在超声照射下，TiC/TiO@CaCO/KAE 通过快速释放 Ca2+、抑制 Ca2+外排、增强肿瘤抑制作用以及将“冷”肿瘤转化为“热”肿瘤等多种作用，对线粒体造成多级损伤。因此，本研究提出了一种通过制备 pH 敏感、双重激活和多功能 TiC/TiO 基纳米系统来有效结合线粒体 Ca 稳态和声动力学治疗（SDT）的方法，用于癌症治疗。
