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多功能治疗性纳米系统实现了光热-化疗联合治疗,具有三重刺激响应性药物释放和磁共振成像功能。

Multifunctional theranostic nanosystems enabling photothermal-chemo combination therapy of triple-stimuli-responsive drug release with magnetic resonance imaging.

机构信息

Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory for Novel Reactor and Green Chemistry Technology, Hubei Engineering Research Center for Advanced Fine Chemicals, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, Wuhan 430205, P.R. China.

The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, P. R. China.

出版信息

Biomater Sci. 2020 Mar 31;8(7):1875-1884. doi: 10.1039/c9bm01482a.

DOI:10.1039/c9bm01482a
PMID:32010912
Abstract

Theranostic nanosystems are emerging as a promising approach for controlled drug delivery, diagnosis and multimodal therapeutics. Herein, a multifunctional theranostic nanoplatform is reported for photothermal-chemo combination therapy functioned with magnetic and thermal imaging. Hyaluronic acid (HA) coated Fe3O4@polydopamine nanoparticles equipped with redox-sensitive disulfide linkers have been subsequently deposited with an anticancer drug, doxorubicin (DOX) (termed as FPCH-DOX NPs). These nanocomposites possess an average diameter of 120 nm, a saturation magnetization of 28.5 emu g-1, DOX loading capacity of 7.13% and a transverse relaxation rate of 171.76 mM-1 s-1. The drug release could be triggered by pH, glutathione (GSH) concentration and light irradiation. Prussian blue staining and confocal microscopy demonstrate that these nanoplatforms have improved biocompatibility and cellular uptake in CD44-positive HeLa cell lines rather than in CD44-negative NIH 3T3 normal cell lines. In vitro evaluations demonstrate that the combination therapy of FPCH-DOX NPs lowers the cell viability to 16.2%, less than that of individual chemotherapy (55.3%) or PTT (52.1%). In vivo MRI indicates that the tumor accumulation of FPCH-DOX NPs provides enhanced MRI contrast, and in vivo thermal imaging verified their localized photothermal conversion effect in tumor tissues. Importantly, FPCH-DOX NPs present remarkable anti-tumor efficacy by photothermal-chemo combination therapy. H&E and Ki67 staining tests show obvious necrosis and weak cell proliferation at the region of the tumor. Thus, FPCH-DOX NPs are promising multifunctional nanoplatforms for highly effective cancer theranostics.

摘要

治疗诊断一体化纳米系统作为一种控制药物输送、诊断和多模式治疗的有前途的方法正在出现。本文报道了一种多功能治疗诊断一体化纳米平台,用于光热-化疗联合治疗,并具有磁共振和热成像功能。透明质酸(HA)包覆的 Fe3O4@聚多巴胺纳米粒子带有氧化还原敏感的二硫键,随后沉积了一种抗癌药物阿霉素(DOX)(称为 FPCH-DOX NPs)。这些纳米复合材料的平均直径为 120nm,饱和磁化强度为 28.5 emu g-1,DOX 载药量为 7.13%,横向弛豫率为 171.76 mM-1 s-1。药物释放可以通过 pH、谷胱甘肽(GSH)浓度和光照射来触发。普鲁士蓝染色和共聚焦显微镜表明,这些纳米平台在 CD44 阳性的 HeLa 细胞系中具有改善的生物相容性和细胞摄取能力,而在 CD44 阴性的 NIH 3T3 正常细胞系中则没有。体外评价表明,FPCH-DOX NPs 的联合治疗将细胞活力降低至 16.2%,低于单独化疗(55.3%)或 PTT(52.1%)。体内 MRI 表明,FPCH-DOX NPs 的肿瘤积累提供了增强的 MRI 对比,体内热成像验证了它们在肿瘤组织中的局部光热转换效应。重要的是,FPCH-DOX NPs 通过光热-化疗联合治疗表现出显著的抗肿瘤疗效。H&E 和 Ki67 染色试验显示肿瘤区域有明显的坏死和较弱的细胞增殖。因此,FPCH-DOX NPs 是用于高效癌症治疗诊断的有前途的多功能纳米平台。

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