Key Laboratory of Inorganic Coating Materials CAS, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China.
Center of Materials Science and Optoelectronics Engineer, University of Chinese Academy of Sciences, Beijing 100049, China.
Biomater Sci. 2024 Jul 23;12(15):3918-3932. doi: 10.1039/d4bm00583j.
The thioredoxin system is involved in cancer development and therefore is a promising target for cancer chemotherapy. Thioredoxin reductase (TrxR) is a key component of the thioredoxin (Trx) system, and is overexpressed in many cancers to inhibit apoptosis-related proteins. Alternatively, inhibition of thioredoxin reductase and upregulation of apoptosis factors provide a therapeutic strategy for anti-tumor treatment. In this study, an ultrasound-activatable -organosilica nanomedicine was prepared by integrating chloroquine (CQ) into hollow mesoporous organosilica (CQ@MOS). The -organosilica nanomedicine can inhibit the activity of thioredoxin reductase, elevate cellular reactive oxygen species (ROS) levels, upregulate the pro-apoptotic factors in the c-Jun N-terminal kinase (JNK) apoptosis pathway and induce autophagy inhibition, further resulting in mitochondrial membrane potential (MMP) depolarization and cellular ATP content decrease, ultimately causing significant damage to tumor cells. Moreover, CQ@MOS can efficiently deliver chloroquine into cancer cells and promote an enhanced sonodynamic effect for effective anti-tumor chemotherapy and sonodynamic therapy. This study may enlighten us on a new anti-tumor strategy and suggest its promising applications in cancer treatments.
硫氧还蛋白系统参与癌症的发生发展，因此是癌症化疗的一个有前途的靶点。硫氧还蛋白还原酶（TrxR）是硫氧还蛋白（Trx）系统的关键组成部分，在许多癌症中过度表达，以抑制与细胞凋亡相关的蛋白。相反，抑制硫氧还蛋白还原酶和上调细胞凋亡因子为抗肿瘤治疗提供了一种治疗策略。在本研究中，通过将氯喹（CQ）整合到中空介孔有机硅（CQ@MOS）中，制备了一种超声激活的-有机硅纳米药物。该-有机硅纳米药物可以抑制硫氧还蛋白还原酶的活性，提高细胞内活性氧（ROS）水平，上调 c-Jun N 末端激酶（JNK）凋亡途径中的促凋亡因子，并诱导自噬抑制，进一步导致线粒体膜电位（MMP）去极化和细胞内 ATP 含量减少，最终导致肿瘤细胞的显著损伤。此外，CQ@MOS 可以有效地将氯喹递送到癌细胞中，并促进增强的声动力学效应，以实现有效的抗肿瘤化疗和声动力学治疗。本研究可能为我们提供一种新的抗肿瘤策略，并暗示其在癌症治疗中的应用前景。
