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基于岩藻依聚糖的双靶向介孔聚多巴胺,通过P-选择素介导的药物递送增强肝癌的MRI引导化学光热疗法。

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

作者信息

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

机构信息

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.

Department of radiology, Lishui Hospital of Zhejiang University, School of Medicine, Lishui 323000, China.

出版信息

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

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/Gd/DOX) was prepared as an effective theranostic agent for magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of HCC. It was found that FMPDA/Gd/DOX had a high photothermal conversion efficiency of 33.4% and excellent T-MRI performance with a longitudinal relaxivity (r) value of 14.966 mM·  . Moreover, the results suggested that FMPDA/Gd/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/Gd/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality. Overall, our study demonstrated that FMPDA/Gd/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics.

摘要

在肝细胞癌(HCC)的治疗中,仍然迫切需要开发具有出色诊断和治疗性能的新型诊疗试剂。在此,制备了一种负载钆铁和阿霉素的岩藻依聚糖修饰的介孔聚多巴胺纳米颗粒(FMPDA/Gd/DOX),作为一种有效的诊疗试剂,用于磁共振成像(MRI)引导下的HCC化学光热疗法。研究发现,FMPDA/Gd/DOX具有33.4%的高光热转换效率和优异的T1-MRI性能,纵向弛豫率(r1)值为14.966 mM-1·s-1。此外,结果表明,FMPDA/Gd/DOX可以通过双重靶向肿瘤浸润血小板和HCC细胞有效地积聚到肿瘤病灶中,这是由于岩藻依聚糖与过表达的p-选择素受体之间的特异性相互作用所致。因此,优异的肿瘤归巢能力和MRI引导的化学光热疗法使FMPDA/Gd/DOX比各自的单一治疗方式具有更强的抑制肿瘤生长的能力。总体而言,我们的研究表明,FMPDA/Gd/DOX可作为一种潜在的纳米平台,用于安全有效的癌症诊疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/affb/9800939/9df7c4aac909/gr1.jpg

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