Sialic acid-engineered mesoporous polydopamine nanoparticles loaded with SPIO and Fe3+ as a novel theranostic agent for T1/T2 dual-mode MRI-guided combined chemo-photothermal treatment of hepatic cancer

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 ([email protected]) was firstly prepared, followed by modifying with a targeted molecule of sialic acid (SA) and chelating with Fe3+ ([email protected]/Fe3+ NPs). After that, doxorubicin (DOX)-loaded [email protected]/Fe3+ NPs ([email protected]/DOX/Fe3+) was prepared for tumor theranostics. The prepared [email protected]/Fe3+ 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 r1 = 4.29 mM−1s−1 and r2 = 105.53 mM−1s−1, respectively. [email protected]/Fe3+ NPs could effectively encapsulate the DOX, showing dual pH- and thermal-triggered drug release behavior. In vitro and in vivo studies revealed that [email protected]/DOX/Fe3+ 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 [email protected]/DOX/Fe3+ NPs with a more precise T1-T2 dual mode contrast imaging effect than the one without SA modification. In addition, [email protected]/DOX/Fe3+ 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 [email protected]/DOX/Fe3+ NPs is an effective targeted nanoplatform for tumor theranostics, having potential value in the effective treatment of hepatic cancer.