超声触发纳米颗粒诱导铜增生以增强免疫原性声动力治疗

IF 27.4 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Jia Huang, Fuzhen Hu, Hanchen Zhang, Zheng Cao, Haihua Xiao, Zhiying Yang, Qionghua Jin, Kun Shang
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引用次数: 0

摘要

cuprotosis作为一种新的细胞死亡机制,在肿瘤治疗中具有重要的应用前景。然而,现有的研究通常采用内源性或外源性途径诱导铜体变形的方法,往往无法在空间和时间上实现精确控制。在此,聚合物纳米颗粒(RC NPs)被开发出来,能够通过声学控制来精确激活铜增生,以进行肿瘤特异性治疗。纳米颗粒是通过可降解的声敏感聚合物(Poly RA)和金属离子可负载的多酚结构聚合物(Poly MPN)的自组装制成的。超声刺激劈裂RC NPs,产生活性氧(ROS),促进Poly MPN中铜离子的释放,导致脂酰化蛋白聚集,铁硫簇蛋白耗竭,导致铜还原。随后,RC NPs成功激活小鼠免疫系统,促进抗原呈递细胞成熟和T淋巴细胞活化。纳米颗粒在原位和患者来源的异种移植(PDX)模型中均表现出良好的生物安全性和显著的肿瘤抑制作用。这些新型纳米颗粒为治疗高侵袭性癌症提供了一种有希望的模式,并为未来的临床应用提供了宝贵的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Ultrasound-Triggered Nanoparticles Induce Cuproptosis for Enhancing Immunogenic Sonodynamic Therapy

Ultrasound-Triggered Nanoparticles Induce Cuproptosis for Enhancing Immunogenic Sonodynamic Therapy
Cuproptosis, as a novel mechanism of cell death, holds significant promise for tumor therapy. However, existing studies typically employ methods to induce cuproptosis through endogenous or exogenous pathways, which often fail to achieve precise control in both space and time. Herein, polymeric nanoparticles (RC NPs) are developed that enable precise activation of cuproptosis through acoustic control for tumor-specific treatment. The nanoparticles are fabricated via self-assembly of a degradable, acoustic-sensitive polymer (Poly RA) and a metal-ion-loadable polyphenol-structured polymer (Poly MPN). Ultrasound stimulation cleaved the RC NPs, generating reactive oxygen species (ROS) and promoting the release of copper ions from Poly MPN, leading to the aggregation of lipoylated proteins and depletion of iron-sulfur cluster proteins to introduce cuproptosis. Subsequently, the RC NPs successfully activated the immune system of mice, promoting the maturation of antigen-presenting cells and the activation of T lymphocytes. The nanoparticles exhibited good biosafety and significant tumor inhibition in both orthotopic and patient-derived xenograft (PDX) models. These novel nanoparticles provide a promising modality for the treatment of highly aggressive cancers and a valuable avenue for future clinical applications.
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来源期刊
Advanced Materials
Advanced Materials 工程技术-材料科学:综合
CiteScore
43.00
自引率
4.10%
发文量
2182
审稿时长
2 months
期刊介绍: Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.
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