A metal-phenolic nanotuner induces cancer pyroptosis for sono-immunotherapy.

IF 5.8 3区 医学 Q1 MATERIALS SCIENCE, BIOMATERIALS
Guohao Wang, Dongmei Wang, Huimin Tian, Lu Xia, Dongyan Shen, Zhanxiang Wang, Yunlu Dai
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引用次数: 0

Abstract

Although ultrasound therapy is efficacious and safe in clinical oncology, its capacity to elicit an anti-tumor immune response is constrained by ultrasound-induced apoptosis. Pyroptosis, which releases immunogenic damage-associated molecular patterns (DAMPs), can significantly enhance immune activation. It necessitates robust Gasdermin E (GSDME) expression in cancer cells for caspase-3-mediated pyroptosis. An epigenetic strategy is introduced to induce cancer pyroptosis during sonotherapy using a nanocoordinator (HTA) constructed through metal-phenolic coordination involving Aza (a DNA methyltransferase inhibitor), TiO2 nanoparticles, and polyphenol-modified hyaluronic acid. While Aza restores GSDME expression, TiO2 generates reactive oxygen species (ROS) under ultrasound stimulation, activating caspase-3 and inducing pyroptosis via GSDME cleavage. In an orthotopic breast cancer model, HTA enhanced anti-tumor immunity and improved the efficacy of sonodynamic therapy (SDT). This approach presents a novel strategy for augmenting SDT through epigenetically induced pyroptosis.

虽然超声波疗法在临床肿瘤学中既有效又安全,但其引起抗肿瘤免疫反应的能力却受到超声波诱导的细胞凋亡的限制。释放免疫原性损伤相关分子模式(DAMPs)的热凋亡可显著增强免疫激活。在癌细胞中,Caspase-3 介导的热凋亡需要强有力的 Gasdermin E(GSDME)表达。本文介绍了一种表观遗传学策略,即在声波疗法过程中使用一种通过金属-酚类配位构建的纳米协调器(HTA)(包括 Aza(一种 DNA 甲基转移酶抑制剂)、TiO2 纳米粒子和多酚修饰的透明质酸)来诱导癌症的热解。在 Aza 恢复 GSDME 表达的同时,TiO2 会在超声刺激下产生活性氧(ROS),激活 Caspase-3,并通过 GSDME 的裂解诱导热凋亡。在正位乳腺癌模型中,HTA 增强了抗肿瘤免疫力,提高了声动力疗法(SDT)的疗效。这种方法提出了一种通过表观遗传诱导的裂解作用增强 SDT 的新策略。
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来源期刊
Biomaterials Science
Biomaterials Science MATERIALS SCIENCE, BIOMATERIALS-
CiteScore
11.50
自引率
4.50%
发文量
556
期刊介绍: Biomaterials Science is an international high impact journal exploring the science of biomaterials and their translation towards clinical use. Its scope encompasses new concepts in biomaterials design, studies into the interaction of biomaterials with the body, and the use of materials to answer fundamental biological questions.
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