Multifunctional nanosheets based on folic acid modified manganese oxide for tumor-targeting theranostic application
Multifunctional nanosheets based on folic acid modified manganese oxide for tumor-targeting theranostic application
复制标题
基于叶酸修饰氧化锰的多功能纳米片用于肿瘤靶向治疗应用
DOI：
10.1088/0957-4484/27/2/025101
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发表时间：
2016-01-15
期刊：
影响因子：
3.5
通讯作者：
Zhang, Yun
中科院分区：
文献类型：
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作者：
Hao, Yongwei;Wang, Lei;Zhang, Yun
非常需要开发具有刺激响应药物释放和诊断成像功能的智能纳米载体用于癌症治疗诊断。在此，我们开发了一种基于可降解二氧化锰 (MnO2) 纳米片的还原和 pH 双重响应肿瘤治疗诊断平台。首先合成尺寸为20-60 nm的MnO2纳米片，并用(3-氨基丙基)三甲氧基硅烷(APTMS)修饰以获得胺功能化的MnO2，然后用NH2-PEG2000-COOH (PEG)功能化。肿瘤靶向基团叶酸 (FA) 最终与聚乙二醇化的 MnO2 纳米片结合。然后，通过物理吸附将化疗剂阿霉素（DOX）负载到修饰的纳米片上，将其命名为MnO2-PEG-FA/DOX。所制备的MnO2-PEG-FA/DOX纳米片具有良好的生物相容性，不仅可以在体外和体内有效地将DOX递送至肿瘤细胞，从而提高抗肿瘤效率，而且还可以响应微酸性环境和高浓度的还原型谷胱甘肽（GSH），导致MnO2降解为锰离子，从而实现磁共振成像（MRI）。在 pH 5.0、含有 2 mM GSH 的情况下，纵向弛豫率 r1 为 2.26 mM−1 s−1。这些还原和 pH 双重响应的生物可降解纳米片结合了高效的 MRI 和化疗，为肿瘤靶向治疗应用提供了一个新颖且有前景的平台。
It is highly desirable to develop smart nanocarriers with stimuli-responsive drug-releasing and diagnostic-imaging functions for cancer theranostics. Herein, we develop a reduction and pH dual-responsive tumor theranostic platform based on degradable manganese dioxide (MnO2) nanosheets. The MnO2 nanosheets with a size of 20–60 nm were first synthesized and modified with (3-Aminopropyl) trimethoxysilane (APTMS) to get amine-functionalized MnO2, and then functionalized by NH2-PEG2000-COOH (PEG). The tumor-targeting group, folic acid (FA), was finally conjugated with the PEGylated MnO2 nanosheets. Then, doxorubicin (DOX), a chemotherapeutic agent, was loaded onto the modified nanosheets through a physical adsorption, which was designated as MnO2-PEG-FA/DOX. The prepared MnO2-PEG-FA/DOX nanosheets with good biocompatibility can not only efficiently deliver DOX to tumor cells in vitro and in vivo, leading to enhanced anti-tumor efficiency, but can also respond to a slightly acidic environment and high concentration of reduced glutathione (GSH), which caused degradation of MnO2 into manganese ions enabling magnetic resonance imaging (MRI). The longitudinal relaxation rate r1 was 2.26 mM−1 s−1 at pH 5.0 containing 2 mM GSH. These reduction and pH dual-responsive biodegradable nanosheets combining efficient MRI and chemotherapy provide a novel and promising platform for tumor-targeting theranostic application.