Fucoidan-based dual-targeting mesoporous polydopamine for enhanced MRI-guided chemo-photothermal therapy of HCC via P-selectin-mediated drug delivery

Gaofeng Shu; Lin Shen; Jiayi Ding; Junchao Yu; Xiaoxiao Chen; Xiaoju Guo; Enqi Qiao; Yaning Chen; Chenying Lu; Zhongwei Zhao; Yongzhong Du; Minjiang Chen; Jiansong Ji

doi:10.1016/j.ajps.2022.08.004

Fucoidan-based dual-targeting mesoporous polydopamine for enhanced MRI-guided chemo-photothermal therapy of HCC via P-selectin-mediated drug delivery

Asian J Pharm Sci. 2022 Nov;17(6):908-923. doi: 10.1016/j.ajps.2022.08.004. Epub 2022 Oct 14.

Authors

Gaofeng Shu^{1

2}, Lin Shen¹, Jiayi Ding¹, Junchao Yu¹, Xiaoxiao Chen², Xiaoju Guo³, Enqi Qiao², Yaning Chen², Chenying Lu^{1

2}, Zhongwei Zhao^{1

2}, Yongzhong Du⁴, Minjiang Chen^{1

2

4}, Jiansong Ji^{1

2}

Affiliations

¹ Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Institute of Imaging Diagnosis and Minimally Invasive Intervention Research, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui 323000, China.
² Department of radiology, Lishui Hospital of Zhejiang University, School of Medicine, Lishui 323000, China.
³ Shaoxing University School of Medcine, Shaoxing 312000, China.
⁴ Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Abstract

The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma (HCC). Here, a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin (FMPDA/Gd³⁺/DOX) was prepared as an effective theranostic agent for magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of HCC. It was found that FMPDA/Gd³⁺/DOX had a high photothermal conversion efficiency of 33.4% and excellent T₁-MRI performance with a longitudinal relaxivity (r₁) value of 14.966 mM^-1·s ^- ¹. Moreover, the results suggested that FMPDA/Gd³⁺/DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells, which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors. The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd³⁺/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality. Overall, our study demonstrated that FMPDA/Gd³⁺/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics.

Keywords: Cancer theranostics; Fucoidan; Mesoporous polydopamine; P-selectin target; Platelets bridge.