Nanospiky Copper Peroxide as Lactate-Modulating Nanoadjuvant To Induce Cuproptosis and Pyroptosis for Enhanced Tumor Immunotherapy.

IF 9.1 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Nano Letters Pub Date : 2025-10-15 DOI:10.1021/acs.nanolett.5c04293

Bin Liu,Xiaorui Chen,Zhiwei Zhen,Jing Li,Pan Zheng,Lili Feng,Shili Gai,Piaoping Yang,Ziyong Cheng,Jun Lin

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引用次数: 0

Abstract

Constructing new types of nanomaterials to enhance antigen presentation and simultaneously reverse the immunosuppressive tumor microenvironment (TME) is crucial to improving the therapeutic effect of tumor immunotherapy. Herein, nanospiky copper peroxide nanoadjuvant has been produced via a straightforward ion substitution process between Cu2+ and calcium carbonate nanoparticles in water followed by reaction with hydrogen peroxide, then loaded with the lactate metabolism regulator fluvastatin sodium and modified with the tumor-targeting molecule hyaluronic acid (defined as NSCuO2@F@HA). The obtained NSCuO2@F@HA nanoparticles not only regulate lactate metabolism by suppressing the extracellular efflux of lactic acid to reverse the immunosuppressive TME but also increase the content of Cu2+ and reactive oxygen species within tumor cells to effectively induce cuproptosis and pyroptosis of tumor cells, further enhancing the presentation of tumor-associated antigens. In consequence, NSCuO2 nanoparticles will offer a powerful reference for nanomaterials serving as therapeutic nanoadjuvants to enhance the efficacy of antitumor immunotherapy.

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纳米氧化铜作为乳酸调节纳米佐剂诱导铜坏死和焦亡以增强肿瘤免疫治疗。

构建新型纳米材料增强抗原呈递，同时逆转免疫抑制肿瘤微环境（TME）是提高肿瘤免疫治疗效果的关键。本研究通过Cu2+和碳酸钙纳米颗粒在水中的直接离子取代过程，与过氧化氢反应，然后负载乳酸代谢调节剂氟伐他汀钠，并用肿瘤靶向分子透明质酸（定义为NSCuO2@F@HA）修饰，制备了纳米尖刺型过氧化铜纳米佐剂。所得NSCuO2@F@HA纳米颗粒不仅通过抑制乳酸的胞外外排来调节乳酸代谢，逆转免疫抑制TME，还可以增加肿瘤细胞内Cu2+和活性氧的含量，有效诱导肿瘤细胞的cuprotosis和pyroptosis，进一步增强肿瘤相关抗原的提呈。因此，NSCuO2纳米颗粒将为纳米材料作为治疗性纳米佐剂来提高抗肿瘤免疫治疗的疗效提供有力的参考。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nano Letters 工程技术-材料科学：综合

CiteScore

16.80

自引率

2.80%

发文量

1182

审稿时长

1.4 months

期刊介绍： Nano Letters serves as a dynamic platform for promptly disseminating original results in fundamental, applied, and emerging research across all facets of nanoscience and nanotechnology. A pivotal criterion for inclusion within Nano Letters is the convergence of at least two different areas or disciplines, ensuring a rich interdisciplinary scope. The journal is dedicated to fostering exploration in diverse areas, including: - Experimental and theoretical findings on physical, chemical, and biological phenomena at the nanoscale - Synthesis, characterization, and processing of organic, inorganic, polymer, and hybrid nanomaterials through physical, chemical, and biological methodologies - Modeling and simulation of synthetic, assembly, and interaction processes - Realization of integrated nanostructures and nano-engineered devices exhibiting advanced performance - Applications of nanoscale materials in living and environmental systems Nano Letters is committed to advancing and showcasing groundbreaking research that intersects various domains, fostering innovation and collaboration in the ever-evolving field of nanoscience and nanotechnology.