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磁共振靶向诊断引导下的 MnO 涂层纳米诊疗剂 LDH 用于协同级联化学/化学动力学癌症治疗。

MnO coated nanotheranostic LDH for synergistic cascade chemo/chemodynamic cancer therapy under the guidance of MRI-targeted diagnosis.

机构信息

State Key Laboratory of Materials Processing and Mold Technology, and Key Laboratory of Materials Chemistry for Energy Conversion and Storage of Ministry of Education (HUST), School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology (HUST), Wuhan 430074, Hubei, PR China.

Radiology department, Wuhan Red Cross Hospital, Wuhan 430074, Hubei, PR China.

出版信息

Biomater Sci. 2022 Mar 2;10(5):1317-1325. doi: 10.1039/d1bm01806j.

Abstract

Integrating magnetic resonance imaging (MRI)-targeted diagnosis with synergistic cascade treatments, such as chemo/chemodynamic therapy (CT/CDT), is highly desired for promoting the antitumor performance; however, the rational design of such "all-in-one" nanomedicine is still in its infancy. In this report, using MnO coated layered dihydroxide (LDH) as a carrier to load chemotherapy molecule 5-flurouracil (5-FU), a novel tumor microenvironment (TME) regulating nanodrug is formed: LDH/5-FU@MnO. Combined guidance of CT/CDT and MRI is used to realize synergistic diagnosis and enhanced anti-tumor efficacy. MnO is converted into Mn in the presence of reducing agent GSH, the generated Mn, not only serves as the chemical fuel for the Fenton reaction, combining HO depletion and ˙OH generation, but can also be used as a nuclear magnetic contrast agent for MRI. Moreover, the tumor acidic environment is able to trigger 5-FU release for initiating chemotherapy in the tumor zone. This "all-in-one" LDH/5-FU@MnO nanomedicine integrating multiple treatment modalities and magnetic resonance imaging properties, causes persistent modulation of the TME and exhibits effective antitumor theranostic performance. Such a sophisticated nanomedicine design not only achieves improved CT/CDT antitumor efficiency, but also realizes the activatable magnetic resonance imaging. This strategy combines the merits of each treatment, significantly enhancing the anticancer efficacy, and is anticipated to display promising potentials in the clinical translation plans.

摘要

将磁共振成像 (MRI) 靶向诊断与协同级联治疗(如化疗/化学动力学治疗 (CT/CDT))相结合,是提高抗肿瘤性能的迫切需求;然而,这种“一体化”纳米药物的合理设计仍处于起步阶段。在本报告中,我们使用 MnO 包覆的层状氢氧化物 (LDH) 作为载体来负载化疗分子 5-氟尿嘧啶 (5-FU),形成了一种新型的肿瘤微环境 (TME) 调节纳米药物:LDH/5-FU@MnO。联合 CT/CDT 和 MRI 指导,实现协同诊断和增强抗肿瘤疗效。在还原剂 GSH 的存在下,MnO 转化为 Mn,生成的 Mn 不仅可以作为 Fenton 反应的化学燃料,结合 HO 的消耗和˙OH 的产生,还可以作为 MRI 的磁共振对比剂。此外,肿瘤酸性环境能够触发 5-FU 释放,从而在肿瘤区域引发化疗。这种集多种治疗方式和磁共振成像性能于一体的“一体化”LDH/5-FU@MnO 纳米药物,持续调节 TME,表现出有效的抗肿瘤治疗效果。这种复杂的纳米药物设计不仅提高了 CT/CDT 的抗肿瘤效率,还实现了磁共振成像的激活。该策略结合了每种治疗方法的优点,显著提高了抗癌疗效,有望在临床转化计划中展现出广阔的应用前景。

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