K2FeO4-Enhanced Photodynamic Therapy of Breast Cancer via In Situ Synthesis of Fe2O3 and O2.

IF 10 2区 医学 Q1 ENGINEERING, BIOMEDICAL Advanced Healthcare Materials Pub Date : 2024-11-02 DOI:10.1002/adhm.202402827
Yi Sun, Xin Peng, Yudong Guan, Tong Su, Zezun Xie, Ziying Wu, Yongxuan Long, Huihui Zhu, Jie Shao, Xiaoli Mai, Xuzhi Shi, Tingting Wu, Zhaogang Teng, Bing Zhang, Kun Chen, Xiaoyan Xin
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Abstract

Photodynamic Therapy (PDT) offers a promising minimally invasive treatment for breast cancer, but its efficacy is limited by the hostile tumor microenvironment (TME), including hypoxia and high glutathione (GSH) levels. Although various strategies to improve oxygen concentration or reduce reactive oxygen species (ROS) resistance for enhanced PDT have been explored, they typically require intricate design and complex synthesis of multifunctional nanocarriers. Thus, this study introduces a facile K2FeO4-induced strategy to enhance PDT efficiency in breast cancer through the tumor in situ synthesis of Fe2O3 and O2. Inspired by the successful application of K2FeO4 in ecological remediation and hemostasis, K2FeO4 reacts with GSH, biological system, H2O2, and water, to generate Fe2O3 and O2. Intratumoral injection of K2FeO4 improves the TME, followed by Ce6 administration to enhance PDT through synergistic ferroptosis. This approach boosts PDT efficacy significantly by increasing ROS generation, lipid peroxidation, and inhibiting GSH and GPX4. Proteomic analysis revealed alterations in key pathways, including endocytosis and energy metabolism. This K2FeO4-PDT strategy creates a positive feedback loop by enhancing oxidative stress, providing an interesting and promising approach to PDT.

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通过原位合成 Fe2O3 和 O2 实现 K2FeO4 增强乳腺癌光动力疗法。
光动力疗法(PDT)为乳腺癌提供了一种前景广阔的微创治疗方法,但其疗效受到恶劣的肿瘤微环境(TME)的限制,包括缺氧和高谷胱甘肽(GSH)水平。虽然人们探索了各种提高氧浓度或降低活性氧(ROS)抗性以增强光动力疗法的策略,但它们通常需要复杂的设计和多功能纳米载体的复杂合成。因此,本研究介绍了一种简便的 K2FeO4 诱导策略,通过在肿瘤原位合成 Fe2O3 和 O2 来提高乳腺癌的 PDT 效率。受 K2FeO4 在生态修复和止血方面成功应用的启发,K2FeO4 与 GSH、生物系统、H2O2 和水反应生成 Fe2O3 和 O2。瘤内注射 K2FeO4 可改善 TME,然后再注射 Ce6,通过协同铁氧化作用增强 PDT。这种方法通过增加 ROS 生成、脂质过氧化以及抑制 GSH 和 GPX4,显著提高了 PDT 的疗效。蛋白质组分析揭示了关键通路的改变,包括内吞和能量代谢。这种 K2FeO4-PDT 策略通过增强氧化应激形成了一个正反馈循环,为 PDT 提供了一种有趣而有前景的方法。
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来源期刊
Advanced Healthcare Materials
Advanced Healthcare Materials 工程技术-生物材料
CiteScore
14.40
自引率
3.00%
发文量
600
审稿时长
1.8 months
期刊介绍: Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.
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