Redox double-switch cancer theranostics through Pt(IV) functionalised manganese dioxide nanostructures.
Redox double-switch cancer theranostics through Pt(IV) functionalised manganese dioxide nanostructures.
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DOI：
10.1039/d3nr00076a
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发表时间：
2023-06-30
期刊：
影响因子：
6.7
通讯作者：
Gallo, Juan
中科院分区：
文献类型：
--
作者：
Brito, Beatriz;Ruggiero, Maria Rosaria;Price, Thomas W.;da Costa Silva, Milene;Genicio, Nuria;Wilson, Annah J.;Tyurina, Olga;Rosecker, Veronika;Eykyn, Thomas R.;Banobre-Lopez, Manuel;Stasiuk, Graeme J.;Gallo, Juan
二氧化锰（MnO2）基纳米结构已成为有前途的肿瘤微环境（TME）响应平台。在此，我们使用一锅反应制备了MnO2纳米结构，其中Pt（iv）复合物作为顺铂（Pt(ii)）（一种临床化疗药物）的前药，Pt（iv）前体药物作为氧化还原（因此TME-）反应治疗癌症。在二维和三维（2D和3D） A549细胞模型中评估了这些MnO2-Pt （iv）探针的细胞毒性，发现在3D模型中与活性药物顺铂一样有效。此外，MnO2-Pt （iv）纳米颗粒对还原剂的反应表现出强烈的off/ON磁共振（MR）对比，抗坏血酸处理后，其纵向弛豫度（r1）增加了136倍。在体外（2D和3D）细胞中也观察到这种关闭/打开的MR开关。体内MRI实验显示，在A549荷瘤小鼠瘤内注射后，纳米结构诱导了强烈而持久的T1信号增强。这些结果表明MnO2-Pt (iv) NPs作为癌症治疗的氧化还原反应性MR治疗药物的潜力。基于锰纳米结构和铂前体药物开发了一种新的氧化还原反应双开关癌症治疗方法。这些探针对氧化还原状态改变的响应能力在2/3D细胞模型和临床前小鼠模型中得到了验证。
Manganese dioxide (MnO2)-based nanostructures have emerged as promising tumour microenvironment (TME) responsive platforms. Herein, we used a one-pot reaction to prepare MnO2 nanostructures with Pt(iv) prodrugs as redox- (and thus TME-) responsive theranostics for cancer therapy, in which the Pt(iv) complexes act as prodrugs of cisplatin (Pt(ii)), a clinical chemotherapeutic drug. The cytotoxicity of these MnO2–Pt(iv) probes was evaluated in two and three dimensional (2D and 3D) A549 cell models and found to be as effective as active drug cisplatin in 3D models. Moreover, MnO2–Pt(iv) nanoparticles exhibited strong off/ON magnetic resonance (MR) contrast in response to reducing agents, with the longitudinal relaxivity (r1) increasing 136-fold upon treatment with ascorbic acid. This off/ON MR switch was also observed in (2D and 3D) cells in vitro. In vivo MRI experiments revealed that the nanostructures induce a strong and long-lasting T1 signal enhancement upon intratumoral injection in A549 tumour-bearing mice. These results show the potential of MnO2–Pt(iv) NPs as redox responsive MR theranostics for cancer therapy. A new redox-responsive double-switch cancer theranostic was developed based on Mn nanostructures and a Pt prodrug. The ability of these probes to respond to altered redox states was validated in 2/3D cell models and in a preclinical mouse model.
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