研究动态
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用于超声放大肝细胞癌治疗和肺转移抑制的超小型酶动力学 PANoptosis 纳米诱导剂。

Ultrasmall Enzyodynamic PANoptosis Nano-Inducers for Ultrasound-Amplified Hepatocellular Carcinoma Therapy and Lung Metastasis Inhibition.

发表日期:2024 Sep 03
作者: Wuyang Wei, Hai Wang, Chunrong Ren, Ruxi Deng, Qiaoxi Qin, Li Ding, Pan Li, Ying Liu, Meiqi Chang, Yu Chen, Yang Zhou
来源: Cell Death & Disease

摘要:

解决当前肝细胞癌治疗方法效率低下的问题是一项紧迫而紧迫的挑战。 PANoptosis 是一种炎症性程序性细胞死亡形式,通过参与多种细胞死亡途径(细胞凋亡、细胞焦亡和坏死性凋亡),提供了一种可靠的抗癌策略。本研究设计了一种具有超声放大多酶模拟特性的超小型 Bi2Sn2O7 纳米酶,作为 PANoptosis 诱导剂,通过破坏肿瘤细胞的线粒体功能,增强细胞内有毒活性氧的积累,最终触发 PANoptosis 过程的激活。 PANoptosis 诱导剂的作用已通过相关蛋白的表达得到验证,包括 cleaved Caspase 3、NLRP3、N-GSDMD、cleaved Caspase 1、p-MLKL 和 RIPK3。外部超声波照射的加入显着提高了酶动力学治疗效率。体外和体内抗肿瘤功效以及对肺转移的抑制,验证了 Bi2Sn2O7 介导的 PANoptosis 途径的益处。这项研究不仅阐明了 Bi2Sn2O7 作为全凋亡诱导剂的复杂机制,而且为肝细胞癌的治疗提供了新的视角。© 2024 Wiley‐VCH GmbH。
Addressing the inefficiency of current therapeutic approaches for hepatocellular carcinoma is an urgent and pressing challenge. PANoptosis, a form of inflammatory programmed cell death, presents a dependable strategy for combating cancer by engaging multiple cell death pathways (apoptosis, pyroptosis, and necroptosis). In this study, an ultrasmall Bi2Sn2O7 nanozyme with ultrasound-magnified multienzyme-mimicking properties is designed and engineered as a PANoptosis inducer through destroying the mitochondrial function of tumor cells and enhancing the intracellular accumulation of toxic reactive oxygen species, finally triggering the activation of PANoptosis process. The role of PANoptosis inducer has been verified by the expression of related proteins, including cleaved Caspase 3, NLRP3, N-GSDMD, cleaved Caspase 1, p-MLKL, and RIPK3. The inclusion of external ultrasonic irradiation significantly augments the enzyodynamic therapeutic efficiency. In vitro and in vivo antineoplastic efficacy, along with inhibition of lung metastasis, validate the benefits of the Bi2Sn2O7-mediated PANoptosis pathway. This study not only elucidates the intricate mechanisms underlying Bi2Sn2O7 as a PANoptosis inducer, but also offers a novel perspective for the treatment of hepatocellular carcinoma.© 2024 Wiley‐VCH GmbH.