Sialic acid-engineered mesoporous polydopamine nanoparticles loaded with SPIO and Fe(3+) as a novel theranostic agent for T1/T2 dual-mode MRI-guided combined chemo-photothermal treatment of hepatic cancer

以唾液酸修饰的介孔聚多巴胺纳米粒子负载超顺磁性氧化铁纳米粒子(SPIO)和Fe(3+)作为新型诊疗一体化试剂,用于T1/T2双模磁共振成像引导的肝癌联合化疗-光热治疗。

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Abstract

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(3+) (SA-MPDA@SPIO/Fe(3+) NPs). After that, doxorubicin (DOX)-loaded SA-MPDA@SPIO/Fe(3+) NPs (SA-MPDA@SPIO/DOX/Fe(3+)) was prepared for tumor theranostics. The prepared SAPEG-MPDA@SPIO/Fe(3+) NPs were water-dispersible and biocompatible as evidenced by MTT assay. In vitro photothermal and relaxivity property suggested that the novel theranostic agent possessed excellent photothermal conversion capability and photostability, with relaxivity of being r(1) = 4.29 mM(-1)s(-1) and r(2) = 105.53 mM(-1)s(-1), respectively. SAPEG-MPDA@SPIO/Fe(3+) NPs could effectively encapsulate the DOX, showing dual pH- and thermal-triggered drug release behavior. In vitro and in vivo studies revealed that SA-MPDA@SPIO/DOX/Fe(3+) 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(3+) 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(3+) 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(3+) NPs is an effective targeted nanoplatform for tumor theranostics, having potential value in the effective treatment of hepatic cancer.

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