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用于乳腺癌化学动力疗法和化疗的阿霉素与铁掺杂介孔二氧化硅纳米粒子

Doxorubicin and Iron-doped Mesoporous Silica Nanoparticles for Chemodynamic Therapy and Chemotherapy of Breast Cancer.

作者信息

Tang Le, Chen Mingjian, Wang Dan, He Yi, Ge Guili, Zeng Zhaoyang, Shu Jinyong, Guo Wenjia, Wu Steven Xu, Xiong Wei

机构信息

Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208 (China).

NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078 (China).

出版信息

New J Chem. 2024 Oct 21;48(39):17294-17309. doi: 10.1039/d4nj03184a. Epub 2024 Sep 27.

Abstract

Breast cancer is one of the most prevalent malignancies, necessitating the exploration of more effective synergistic treatment strategies to overcome the limitations of conventional therapies. Chemodynamic therapy (CDT) is an innovative antitumor approach that can be combined with chemotherapy to achieve potent synergistic effects. Mesoporous silica nanomaterials (MSNs) are ideal drug delivery vehicles in cancer therapy due to their unique advantages. This study presents an effective and straightforward strategy to design an intelligent drug delivery system (DDS) activated by the tumor-specific weakly acidic microenvironment to achieve efficient cancer treatment. By incorporating the chemotherapeutic drug doxorubicin (DOX) and divalent iron (Fe) into the unique mesoporous channels of MSNs, we fabricated MSNs@Fe@DOX. Under weakly acidic pH conditions, the functional components Fe and DOX of MSNs@Fe@DOX are gradually released at the tumor site. The released Fe can then consume hydrogen peroxide (HO) in tumor cells, increasing the levels of reactive oxygen species (ROS) and lipid peroxides through the Fenton reaction, thereby inducing ferroptosis. The combination of DOX-induced apoptosis and ferroptosis results in further enhanced cancer treatment. and experiments demonstrated that MSNs@Fe@DOX had an excellent therapeutic effect on breast cancer cells and tumor-bearing nude mice. We anticipate that this study will provide a promising biotechnological platform for combined breast cancer treatment by inducing CDT and chemotherapy.

摘要

乳腺癌是最常见的恶性肿瘤之一,因此需要探索更有效的协同治疗策略来克服传统疗法的局限性。化学动力疗法(CDT)是一种创新的抗肿瘤方法,可与化疗联合以实现强大的协同效应。介孔二氧化硅纳米材料(MSNs)因其独特优势,是癌症治疗中理想的药物递送载体。本研究提出了一种有效且简便的策略,设计一种由肿瘤特异性弱酸性微环境激活的智能药物递送系统(DDS),以实现高效的癌症治疗。通过将化疗药物阿霉素(DOX)和二价铁(Fe)纳入MSNs独特的介孔通道中,我们制备了MSNs@Fe@DOX。在弱酸性pH条件下,MSNs@Fe@DOX的功能成分Fe和DOX在肿瘤部位逐渐释放。释放出的Fe随后可消耗肿瘤细胞中的过氧化氢(HO),通过芬顿反应增加活性氧(ROS)和脂质过氧化物的水平,从而诱导铁死亡。DOX诱导的凋亡与铁死亡相结合,导致癌症治疗效果进一步增强。 和 实验表明,MSNs@Fe@DOX对乳腺癌细胞和荷瘤裸鼠具有优异的治疗效果。我们预计本研究将为通过诱导CDT和化疗联合治疗乳腺癌提供一个有前景的生物技术平台。

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