Lin Li, Guanheng Wang, Biao Xue, Xueao Li, Jiapeng Wang, Wenjun Wang, Chang Liu*, Chunlei Li* and Xiuwen Zheng*,
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引用次数: 0
摘要
我们设计了l/d-Cu/Z@MH，这是一种多模态治疗纳米平台，由透明质酸（HA）和手性氨基酸功能化，以增强肿瘤靶向特异性和细胞内化。纳米颗粒表现出ph响应降解，在细胞摄取后迅速释放Cu2+和MnO2层。这些药物与内源性H2O2驱动肿瘤微环境（TME）放大的芬顿样反应，产生细胞毒性活性氧（ROS），消耗谷胱甘肽，增强化学动力学治疗（CDT）。铜离子诱导cuprotosis，而锰离子激活cGAS-STING信号通路。协同作用下，ROS过量产生和cGAS-STING激活可引起内质网应激和免疫原性细胞死亡（ICD），有效地重新编程肿瘤的免疫抑制微环境。本研究结果表明，l/d-Cu/Z@MH纳米颗粒具有较强的肿瘤抑制作用，其中l- cu /Z@MH具有较好的抑制效果。
A Chiral Amino Acid-Modified pH-Responsive Nanoplatform Coactivates Cuproptosis and cGAS-STING Signaling Pathways for Cancer Therapy
We engineered l/d-Cu/Z@MH, a multimodal therapeutic nanoplatform functionalized with hyaluronic acid (HA) and chiral amino acids, to enhance tumor-targeting specificity and cellular internalization. The nanoparticles exhibit pH-responsive degradation, rapidly releasing Cu2+ and MnO2 layers upon cellular uptake. These agents drive a tumor microenvironment (TME)-amplified Fenton-like reaction with endogenous H2O2, generating cytotoxic reactive oxygen species (ROS), depleting glutathione, and augmenting chemodynamic therapy (CDT). Copper ions induce cuproptosis, while manganese ions activate the cGAS-STING signaling pathway. Synergistically, ROS overproduction and cGAS-STING activation provoke endoplasmic reticulum stress and immunogenic cell death (ICD), effectively reprogramming the tumor’s immunosuppressive microenvironment. The results of this study demonstrated potent tumor suppression by l/d-Cu/Z@MH nanoparticles, with l-Cu/Z@MH showing superior efficacy.
期刊介绍：
ACS Materials Letters is a journal that publishes high-quality and urgent papers at the forefront of fundamental and applied research in the field of materials science. It aims to bridge the gap between materials and other disciplines such as chemistry, engineering, and biology. The journal encourages multidisciplinary and innovative research that addresses global challenges. Papers submitted to ACS Materials Letters should clearly demonstrate the need for rapid disclosure of key results. The journal is interested in various areas including the design, synthesis, characterization, and evaluation of emerging materials, understanding the relationships between structure, property, and performance, as well as developing materials for applications in energy, environment, biomedical, electronics, and catalysis. The journal has a 2-year impact factor of 11.4 and is dedicated to publishing transformative materials research with fast processing times. The editors and staff of ACS Materials Letters actively participate in major scientific conferences and engage closely with readers and authors. The journal also maintains an active presence on social media to provide authors with greater visibility.
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