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负载硫化铜纳米颗粒和顺铂前药共轭的铁(III)-金属有机框架用于磁共振成像引导下的化疗与近红外二区光热疗法联合治疗

CuS Nanoparticles-Loaded and Cisplatin Prodrug Conjugated Fe(III)-MOFs for MRI-Guided Combination of Chemotherapy and NIR-II Photothermal Therapy.

作者信息

Qiang Sufeng, Hu Xiaochun, Li Ruihao, Wu Wenjing, Fang Kang, Li Hui, Sun Yanting, Liang Shujing, Zhao Wenrong, Wang Mengjie, Lin Yun, Shi Shuo, Dong Chunyan

机构信息

Breast Cancer Center, East Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, People's Republic of China.

出版信息

ACS Appl Mater Interfaces. 2022 Aug 17;14(32):36503-36514. doi: 10.1021/acsami.2c12727. Epub 2022 Aug 4.

Abstract

Ovarian cancer has become an urgent threat to global female healthcare. Cisplatin, as the traditional chemotherapeutic agent against ovarian cancer, retains several limitations, such as drug resistance and dose-limiting toxicity. In order to solve the above problems and promote the therapeutic effect of chemotherapy, combining chemotherapy and phototherapy has aroused wide interest. In this study, we constructed a versatile cisplatin prodrug-conjugated therapeutic platform based on ultrasmall CuS-modified Fe(III)-metal-organic frameworks (MIL-88) (named M-Pt/PEG-CuS) for tumor-specific enhanced synergistic chemo-/phototherapy. After intravenous injection, M-Pt/PEG-CuS presented obvious accumulation in tumor and Fe(III)-MOFs possessed magnetic resonance imaging (MRI) to guide synergy therapy. Both in vitro and in vivo experimental results showed that M-Pt/PEG-CuS could not only successfully inhibit tumor growth by combining chemotherapy and NIR-II PTT but also avoid the generation of liver damage by the direct treatment of cisplatin(II). Our work presented the development of the nanoplatform as a novel NIR-II photothermal agent, as well as gave a unique combined chemo-photothermal therapy strategy, which might provide new ways of ovarian cancer therapy for clinical translation.

摘要

卵巢癌已成为全球女性医疗保健的紧迫威胁。顺铂作为传统的抗卵巢癌化疗药物,存在一些局限性,如耐药性和剂量限制性毒性。为了解决上述问题并提高化疗疗效,化疗与光疗相结合引起了广泛关注。在本研究中,我们构建了一种基于超小 CuS 修饰的 Fe(III)金属有机框架(MIL-88)(命名为 M-Pt/PEG-CuS)的多功能顺铂前药共轭治疗平台,用于肿瘤特异性增强协同化疗/光疗。静脉注射后,M-Pt/PEG-CuS 在肿瘤中呈现明显的蓄积,且 Fe(III)金属有机框架具有磁共振成像(MRI)以指导协同治疗。体外和体内实验结果均表明,M-Pt/PEG-CuS 不仅可通过联合化疗和近红外二区光热疗法(NIR-II PTT)成功抑制肿瘤生长,还可避免顺铂直接治疗所产生的肝损伤。我们的工作展示了该纳米平台作为一种新型近红外二区光热剂的研发成果,同时给出了一种独特的联合化疗-光热疗法策略,这可能为卵巢癌治疗的临床转化提供新途径。

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