Shu Gaofeng, Chen Minjiang, Song Jingjing, Xu Xiaoling, Lu Chenying, Du Yuyin, Xu Min, Zhao Zhongwei, Zhu Minxia, Fan Kai, Fan Xiaoxi, Fang Shiji, Tang Bufu, Dai Yiyang, Du Yongzhong, Ji Jiansong
Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital of Zhejiang University, School of Medicine, Lishui, Zhejiang, 323000, China.
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
Bioact Mater. 2020 Nov 10;6(5):1423-1435. doi: 10.1016/j.bioactmat.2020.10.020. eCollection 2021 May.
Hepatic cancer is a serious disease with high morbidity and mortality. Theranostic agents with effective diagnostic and therapeutic capability are highly needed for the treatment of hepatic cancer. Herein, we aimed to develop a novel mesoporous polydopamine (MPDA)-based theranostic agent for T1/T2 dual magnetic resonance imaging (MRI)-guided cancer chemo-photothermal therapy. Superparamagnetic iron oxide (SPIO)-loaded MPDA NPs (MPDA@SPIO) was firstly prepared, followed by modifying with a targeted molecule of sialic acid (SA) and chelating with Fe (SA-MPDA@SPIO/Fe NPs). After that, doxorubicin (DOX)-loaded SA-MPDA@SPIO/Fe NPs (SA-MPDA@SPIO/DOX/Fe) was prepared for tumor theranostics. The prepared SAPEG-MPDA@SPIO/Fe NPs were water-dispersible and biocompatible as evidenced by MTT assay. photothermal and relaxivity property suggested that the novel theranostic agent possessed excellent photothermal conversion capability and photostability, with relaxivity of being r = 4.29 mMs and r = 105.53 mMs, respectively. SAPEG-MPDA@SPIO/Fe NPs could effectively encapsulate the DOX, showing dual pH- and thermal-triggered drug release behavior. and studies revealed that SA-MPDA@SPIO/DOX/Fe NPs could effectively target to the hepatic tumor tissue, which was possibly due to the specific interaction between SA and the overexpressed E-selectin. This behavior also endowed SA-MPDA@SPIO/DOX/Fe NPs with a more precise T1-T2 dual mode contrast imaging effect than the one without SA modification. In addition, SAPEG-MPDA@SPIO/DOX/Fe NPs displayed a superior therapeutic effect, which was due to its active targeting ability and combined effects of chemotherapy and photothermal therapy. These results demonstrated that SAPEG-MPDA@SPIO/DOX/Fe NPs is an effective targeted nanoplatform for tumor theranostics, having potential value in the effective treatment of hepatic cancer.
肝癌是一种发病率和死亡率都很高的严重疾病。治疗肝癌非常需要具有有效诊断和治疗能力的诊疗试剂。在此，我们旨在开发一种基于新型介孔聚多巴胺（MPDA）的诊疗试剂，用于T1/T2双磁共振成像（MRI）引导的癌症化学-光热治疗。首先制备了负载超顺磁性氧化铁（SPIO）的MPDA纳米粒子（MPDA@SPIO），然后用唾液酸（SA）靶向分子进行修饰并与铁螯合（SA-MPDA@SPIO/Fe纳米粒子）。之后，制备了负载阿霉素（DOX）的SA-MPDA@SPIO/Fe纳米粒子（SA-MPDA@SPIO/DOX/Fe）用于肿瘤诊疗。MTT试验证明，所制备的SA-MPDA@SPIO/Fe纳米粒子具有水分散性和生物相容性。光热和弛豫特性表明，这种新型诊疗试剂具有优异的光热转换能力和光稳定性，弛豫率分别为r = 4.29 mM/s和r = 105.53 mM/s。SA-MPDA@SPIO/Fe纳米粒子能够有效地包封DOX，呈现出双pH和热触发药物释放行为。体外和体内研究表明，SA-MPDA@SPIO/DOX/Fe纳米粒子能够有效地靶向肝肿瘤组织，这可能是由于SA与过表达的E-选择素之间的特异性相互作用。这种行为还赋予了SA-MPDA@SPIO/DOX/Fe纳米粒子比未修饰SA的纳米粒子更精确的T1-T2双模对比成像效果。此外，SA-MPDA@SPIO/DOX/Fe纳米粒子显示出优异的治疗效果，这归因于其主动靶向能力以及化疗和光热治疗的联合作用。这些结果表明，SA-MPDA@SPIO/DOX/Fe纳米粒子是一种有效的肿瘤诊疗靶向纳米平台，在肝癌的有效治疗中具有潜在价值。
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