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索拉非尼偶联锌酞菁纳米胶囊用于荷肝癌原位移植瘤小鼠模型的多模式治疗。

Sorafenib-Conjugated Zinc Phthalocyanine Based Nanocapsule for Trimodal Therapy in an Orthotopic Hepatocellular Carcinoma Xenograft Mouse Model.

机构信息

Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China.

Shanghai Institute of Liver Disease, Shanghai 200032, China.

出版信息

ACS Appl Mater Interfaces. 2020 Apr 15;12(15):17193-17206. doi: 10.1021/acsami.0c00375. Epub 2020 Apr 2.

Abstract

Sorafenib, a multitargeted kinase inhibitor, has been reported to elicit a limited therapeutic effect in hepatocellular carcinoma (HCC). Currently, phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is emerging as a powerful modality for cancer therapy. However, few studies have been reported the effectiveness of the combination of sorafenib with PDT and PTT in HCC. Herein, we designed and synthesized bovine serum albumin (BSA)-coated zinc phthalocyanine (ZnPc) and sorafenib (SFB) nanoparticle (ZnPc/SFB@BSA). The obtained ZnPc/SFB@BSA was able to trigger PDT, PTT, and chemotherapy. After irradiation by a 730 nm light, ZnPc/SFB@BSA significantly suppressed HCC cell proliferation and metastasis while promoted cell apoptosis in vitro. Furthermore, intravenous injection of ZnPc/SFB@BSA led to dramatically reduced tumor growth in an orthotopic xenograft HCC model. More importantly, ZnPc/SFB@BSA presented low toxicity and adequate blood compatibility. Therefore, a combination of ZnPc with sorafenib via BSA-assembled nanoparticle can markedly suppress HCC growth, representing a promising strategy for HCC patients.

摘要

索拉非尼是一种多靶点激酶抑制剂,已被报道在肝细胞癌 (HCC) 中产生有限的治疗效果。目前,光疗,包括光动力疗法 (PDT) 和光热疗法 (PTT),正在成为癌症治疗的一种强大手段。然而,很少有研究报道索拉非尼与 PDT 和 PTT 联合用于 HCC 的疗效。在这里,我们设计并合成了牛血清白蛋白 (BSA) 包覆的锌酞菁 (ZnPc) 和索拉非尼 (SFB) 纳米粒子 (ZnPc/SFB@BSA)。所得的 ZnPc/SFB@BSA 能够引发 PDT、PTT 和化学治疗。在 730nm 光照射后,ZnPc/SFB@BSA 显著抑制 HCC 细胞增殖和转移,同时促进细胞凋亡。此外,静脉注射 ZnPc/SFB@BSA 导致原位异种移植 HCC 模型中的肿瘤生长显著减少。更重要的是,ZnPc/SFB@BSA 表现出低毒性和足够的血液相容性。因此,通过 BSA 组装的纳米粒子将 ZnPc 与索拉非尼结合可以显著抑制 HCC 的生长,为 HCC 患者提供了一种有前途的治疗策略。

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