An Acid-Responsive Iron-Based Nanocomposite for OSCC Treatment

IF 8.3 2区材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY

ACS Applied Materials & Interfaces Pub Date : 2024-04-30 DOI:10.1177/00220345241238154

X. Zhao, D. Leng, H. Wang, H. Jin, Y. Wu, Z. Qin, D. Wu, X. Wei

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引用次数: 0

Abstract

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer, characterized by invasiveness, local lymph node metastasis, and poor prognosis. Traditional treatment and medications have limitations, making the specific inhibition of OSCC growth, invasion, and metastasis a challenge. The tumor microenvironment exhibits mildly acidity and high concentrations of H2O2, and its exploitation for cancer treatment has been widely researched across various cancers, but research in the oral cancer field is relatively limited. In this study, by loading ultra-small Prussian blue nanoparticles (USPBNPs) into mesoporous calcium–silicate nanoparticles (MCSNs), we developed an acid-responsive iron-based nanocomposite, USPBNPs@MCSNs (UPM), for the OSCC treatment. UPM demonstrated excellent dual enzyme activities, generating toxic ·OH in a mildly acidic environment, effectively killing OSCC cells and producing O2 in a neutral environment to alleviate tissue hypoxia. The results showed that UPM could effectively inhibit the proliferation, migration, and invasion of OSCC cells, as well as the growth of mice solid tumors, without obvious systemic toxicity. The mechanisms may involve UPM inducing ferroptosis of OSCC cells by downregulating the xCT/GPX4/glutathione (GSH) axis, characterized by intracellular iron accumulation, reactive oxygen species accumulation, GSH depletion, lipid peroxidation, and abnormal changes in mitochondrial morphology. Therefore, this study provides empirical support for ferroptosis as an emerging therapeutic target for OSCC and offers a valuable insight for future OSCC treatment.

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用于治疗 OSCC 的酸响应铁基纳米复合材料

口腔鳞状细胞癌（OSCC）是最常见的口腔癌，具有侵袭性、局部淋巴结转移和预后不良等特点。传统的治疗方法和药物存在局限性，因此如何特异性地抑制 OSCC 的生长、侵袭和转移成为一项挑战。肿瘤微环境呈现弱酸性和高浓度的 H2O2，利用 H2O2 治疗癌症已在各种癌症中得到广泛研究，但在口腔癌领域的研究相对有限。在本研究中，我们将超小普鲁士蓝纳米颗粒（USPBNPs）载入介孔硅酸钙纳米颗粒（MCSNs），开发了一种酸响应铁基纳米复合材料 USPBNPs@MCSNs（UPM），用于治疗口腔癌。UPM 表现出优异的双酶活性，在弱酸性环境中产生有毒的 -OH，有效杀死 OSCC 细胞；在中性环境中产生 O2，缓解组织缺氧。结果表明，UPM 能有效抑制 OSCC 细胞的增殖、迁移和侵袭，以及小鼠实体瘤的生长，且无明显的全身毒性。其机制可能是UPM通过下调xCT/GPX4/谷胱甘肽（GSH）轴诱导OSCC细胞铁变态反应，表现为细胞内铁积累、活性氧积累、GSH耗竭、脂质过氧化和线粒体形态异常变化。因此，本研究为铁变态反应作为OSCC的一个新兴治疗靶点提供了实证支持，并为未来OSCC的治疗提供了有价值的见解。

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

ACS Applied Materials & Interfaces 工程技术-材料科学：综合

CiteScore

16.00

自引率

6.30%

发文量

4978

审稿时长

1.8 months

期刊介绍： ACS Applied Materials & Interfaces is a leading interdisciplinary journal that brings together chemists, engineers, physicists, and biologists to explore the development and utilization of newly-discovered materials and interfacial processes for specific applications. Our journal has experienced remarkable growth since its establishment in 2009, both in terms of the number of articles published and the impact of the research showcased. We are proud to foster a truly global community, with the majority of published articles originating from outside the United States, reflecting the rapid growth of applied research worldwide.