A pH-Responsive Yolk-Like Nanoplatform for Tumor Targeted Dual-Mode Magnetic Resonance Imaging and Chemotherapy
A pH-Responsive Yolk-Like Nanoplatform for Tumor Targeted Dual-Mode Magnetic Resonance Imaging and Chemotherapy
复制标题
用于肿瘤靶向双模磁共振成像和化疗的 pH 响应型蛋黄样纳米平台。
DOI：
10.1021/acsnano.7b02675
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发表时间：
2017-07-01
期刊：
影响因子：
17.1
通讯作者：
Wu, Zhengyan
中科院分区：
文献类型：
--
作者：
Sun, Xiao;Du, Ruohong;Wu, Zhengyan
将T1和T2造影剂结合在一个纳米系统中，发挥各自的MR造影剂作用，同时作为一种有效的药物传递系统（DDS），在癌症的临床诊断和化疗中具有重要的潜在应用。然而，不适当的掺入总是会遇到许多问题，如T1造影剂与水质子的接触面积小，T2造影剂与水分子的距离不合适，T2造影剂对T1成像的干扰等。这些问题严重限制了T1或T2的对比效果。在这项工作中，我们开发了一种由聚乙二醇和叶酸（FA）功能化的蛋黄状Fe3O4@Gd2O3纳米平台，可以有效地发挥其肿瘤靶向T1-T2双模MR成像和药物递送作用。首先，该纳米平台具有较高的纵向弛豫率（r1） （7.91 mM-1 s-1）和较强的横向弛豫率（r2） （386.5 mM-1 s-1），高于原始Fe3O4 （268.1 mM-1 s-1）。其次，顺铂可以有效地加载到纳米平台（112 mg/g），并表现出ph响应释放行为。第三，该纳米平台可被HeLa细胞有效内化，且具有时间依赖性和剂量依赖性。第四，FA受体介导的纳米平台在体外和体内均表现出优异的T1-T2双模式MR对比增强和抗癌活性。第五，在体内系统递送纳米平台没有观察到对重要器官的明显毒性。因此，该纳米平台可能成为肿瘤靶向T1-T2双模MR成像和化疗的潜在纳米治疗手段。
Incorporation of T1 and T2 contrast material in one nanosystem performing their respective MR contrast role and simultaneously serving as an efficient drug delivery system (DDS) has a significant potential application for clinical diagnosis and chemotherapy of cancer. However, inappropriate incorporation always encountered many issues, such as low contact area of T1 contrast material with water-proton, inappropriate distance between T2 contrast material and water molecule, and undesirable disturbance of T2 contrast material for T1 imaging. Those issues seriously limited the T1 or T2 contrast effect. In this work, we developed a yolk-like Fe3O4@Gd2O3 nanoplatform functionalized by polyethylene glycol and folic acid (FA), which could efficiently exert their tumor targeted T1-T2 dual-mode MR imaging and drug delivery role. First, this nanoplatform possessed a high longitudinal relaxation rate (r1) (7.91 mM-1 s-1) and a stronger transverse relaxation rate (r2) (386.5 mM-1 s-1) than that of original Fe3O4 (268.1 mM-1 s-1). Second, cisplatin could be efficiently loaded into this nanoplatform (112 mg/g) and showed pH-responsive release behavior. Third, this nanoplatform could be effectively internalized by HeLa cells with time and dosage dependence. Fourth, the FA receptor-mediated nanoplatform displayed excellent T1-T2 dual mode MR contrast enhancement and anticancer activity both in vitro and in vivo. Fifth, no apparent toxicity for vital organs was observed with systemic delivery of the nanoplatform in vivo. Thus, this nanoplatform could be a potential nanotheranostic for tumor targeted T1-T2 dual-mode MR imaging and chemotherapy.