A “Ferroptosis-Amplifier” Hydrogel for Eliminating Refractory Cancer Stem Cells Post-lumpectomy

IF 9.6 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Nano Letters Pub Date : 2024-06-17 DOI:10.1021/acs.nanolett.4c02192

Yutong Zhu, Xi Deng, Zideng Dai, Qing Liu, Yichen Kuang, Tianzhi Liu* and Hangrong Chen*,

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Abstract

The unique “Iron Addiction” feature of cancer stem cells (CSCs) with tumorigenicity and plasticity generally contributes to the tumor recurrence and metastasis after a lumpectomy. Herein, a novel “Ferroptosis Amplification” strategy is developed based on integrating gallic acid-modified FeOOH (GFP) and gallocyanine into Pluronic F-127 (F127) and carboxylated chitosan (CC)-based hydrogel for CSCs eradication. This “Ferroptosis Amplifier” hydrogel is thermally sensitive and achieves rapid gelation at the postsurgical wound in a breast tumor model. Specifically, gallocyanine, as the Dickkopf-1 (DKK1) inhibitor, can decrease the expression of SLC7A11 and GPX4 and synergistically induce ferroptosis of CSCs with GFP. Encouragingly, it is found that this combination suppresses the migratory and invasive capability of cancer cells via the downregulation of matrix metalloproteinase 7 (MMP7). The in vivo results further confirm that this “Ferroptosis Amplification” strategy is efficient in preventing tumor relapse and lung metastasis, manifesting an effective and promising postsurgical treatment for breast cancer.

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一种用于消除肿瘤切除术后难治性癌症干细胞的 "铁突变-增殖 "水凝胶

癌症干细胞（CSCs）具有独特的 "铁瘾 "特征，具有致瘤性和可塑性，通常会导致肿瘤切除术后的复发和转移。本文基于将没食子酸修饰的FeOOH（GFP）和没食子色素整合到基于Pluronic F-127（F127）和羧基壳聚糖（CC）的水凝胶中，开发出一种新型的 "铁嗜性放大 "策略，用于消灭癌干细胞。这种 "铁突变放大器 "水凝胶对热敏感，可在乳腺肿瘤模型的手术后伤口处快速凝胶化。具体来说，五倍子菁作为Dickkopf-1（DKK1）抑制剂，可以降低SLC7A11和GPX4的表达，并协同诱导带有GFP的CSCs铁突变。令人鼓舞的是，研究还发现这种组合能通过下调基质金属蛋白酶 7（MMP7）抑制癌细胞的迁移和侵袭能力。体内研究结果进一步证实，这种 "铁突变放大 "策略能有效防止肿瘤复发和肺转移，是一种有效且有前景的乳腺癌术后治疗方法。

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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.