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体内评估氧化多壁碳纳米管介导的乳腺癌热疗。

In vivo evaluation of oxidized multiwalled-carbon nanotubes-mediated hyperthermia treatment for breast cancer.

机构信息

Department of Bioscience, Faculty of Science, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor, Malaysia.

Department of Bioscience, Faculty of Science, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor, Malaysia; Cancer and Infectious Diseases Research Group, Health and Wellness Research Alliance, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor, Malaysia.

出版信息

Biomater Adv. 2022 Mar;134:112586. doi: 10.1016/j.msec.2021.112586. Epub 2021 Dec 8.

Abstract

Breast cancer is one of the most common types of cancer that contribute to high mortality worldwide. Hyperthermia (HT) was introduced as one of the alternative treatments to treat breast cancer but has major drawback of damaging normal adjacent cells. This study explores the integration effect of multiwalled‑carbon nanotubes (MWCNTs) in combination with hyperthermia treatment for breast cancer therapy regimes. In this study, acid-functionalized MWCNTs (ox-MWCNTs) were prepared by acid washing methods using HSO/HNO (98%/68%) with the ratio of 3:1 (ν/ν) and characterized by colloidal dispersibility test, FTIR, TGA, XRD, FESEM and EDX analysis. EMT6 tumor-bearing mice were treated with ox-MWCNTs in combination with local HT at 43 °C. The tumor progression was monitored and the influence of immune response was evaluated. Results from this study demonstrated that mice from ox-MWCNTs in combination with local HT treatment group experienced complete tumor eradication, accompanied by a significant increase in median survival of the mice. Histological and immunohistochemical analysis of tumor tissues revealed that tumor treated with combined treatment underwent cell necrosis and there was a significant reduction of proliferating cells when compared to the untreated tumor. This observation is also accompanied with an increase in Hsp70 expression in tumor treated with HT. Flow cytometry analysis of the draining lymph nodes showed an increase in dendritic cells infiltration and maturation in mice treated with combined treatment. In addition, a significant increase of tumor-infiltrated CD8 and CD4 T cells along with macrophages and natural killer cells was observed in tumor treated with combined treatment. Altogether, results presented in this study suggested the potential of ox-MWCNTs-mediated HT as an anticancer therapeutic agent, hence might be beneficial in the future of breast cancer treatment.

摘要

乳腺癌是全球导致高死亡率的最常见癌症类型之一。热疗 (HT) 被引入作为治疗乳腺癌的替代治疗方法之一,但存在损害正常相邻细胞的主要缺点。本研究探讨了将多壁碳纳米管 (MWCNTs) 与 HT 治疗相结合在乳腺癌治疗方案中的综合效应。在这项研究中,通过使用 HSO/HNO (98%/68%) 以 3:1 (ν/ν) 的比例进行酸洗涤方法制备了酸功能化的 MWCNTs (ox-MWCNTs),并通过胶体分散性测试、FTIR、TGA、XRD、FESEM 和 EDX 分析进行了表征。将 ox-MWCNTs 与 43°C 的局部 HT 结合用于 EMT6 荷瘤小鼠的治疗。监测肿瘤进展并评估免疫反应的影响。这项研究的结果表明,ox-MWCNTs 与局部 HT 联合治疗组的小鼠经历了完全的肿瘤消除,同时小鼠的中位生存期显著延长。肿瘤组织的组织学和免疫组织化学分析表明,与未治疗的肿瘤相比,联合治疗的肿瘤经历了细胞坏死,增殖细胞显著减少。这种观察结果还伴随着 HT 治疗的肿瘤中 Hsp70 表达的增加。对引流淋巴结的流式细胞术分析表明,与未治疗的肿瘤相比,联合治疗的小鼠中树突状细胞浸润和成熟增加。此外,在联合治疗的肿瘤中还观察到肿瘤浸润的 CD8 和 CD4 T 细胞以及巨噬细胞和自然杀伤细胞的显著增加。总之,本研究结果表明 ox-MWCNTs 介导的 HT 作为一种抗癌治疗剂的潜力,因此可能对未来的乳腺癌治疗有益。

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