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

Gaofeng Shu; Minjiang Chen; Jingjing Song; Xiaoling Xu; Chenying Lu; Yuyin Du; Min Xu; Zhongwei Zhao; Minxia Zhu; Kai Fan; Xiaoxi Fan; Shiji Fang; Bufu Tang; Yiyang Dai; Yongzhong Du; Jiansong Ji

doi:10.1016/j.bioactmat.2020.10.020

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

Bioact Mater. 2020 Nov 10;6(5):1423-1435. doi: 10.1016/j.bioactmat.2020.10.020. eCollection 2021 May.

Authors

Gaofeng Shu^{1

2}, Minjiang Chen¹, Jingjing Song¹, Xiaoling Xu², Chenying Lu¹, Yuyin Du³, Min Xu¹, Zhongwei Zhao¹, Minxia Zhu², Kai Fan¹, Xiaoxi Fan¹, Shiji Fang¹, Bufu Tang¹, Yiyang Dai⁴, Yongzhong Du², Jiansong Ji¹

Affiliations

¹ Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital of Zhejiang University, School of Medicine, Lishui, Zhejiang, 323000, China.
² Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China.
³ Department of Chemistry, Faculty of Science, Tohoku University, Sendai, 980-8577, Japan.
⁴ Department of Gastroenterology, The Fourth Affiliated Hospital of Zhejiang University, School of Medicine, 32200, YiWu, China.

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 Fe³⁺ (SA-MPDA@SPIO/Fe³⁺ NPs). After that, doxorubicin (DOX)-loaded SA-MPDA@SPIO/Fe³⁺ NPs (SA-MPDA@SPIO/DOX/Fe³⁺) was prepared for tumor theranostics. The prepared SAPEG-MPDA@SPIO/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. SAPEG-MPDA@SPIO/Fe³⁺ 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/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 SA-MPDA@SPIO/DOX/Fe³⁺ NPs with a more precise T1-T2 dual mode contrast imaging effect than the one without SA modification. In addition, SAPEG-MPDA@SPIO/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 SAPEG-MPDA@SPIO/DOX/Fe³⁺ NPs is an effective targeted nanoplatform for tumor theranostics, having potential value in the effective treatment of hepatic cancer.

Keywords: Chemo-photothermal combined therapy; Hepatic cancer; Mesoporous polydopamine; T1/T2 dual-mode MRI; Targeted delivery.