Combination of Peglated-H1/HGFK1 Nanoparticles and TAE in the Treatment of Hepatocellular Carcinoma

聚乙二醇化H1/HGFK1纳米粒子联合TAE治疗肝细胞癌

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作者:Dazhi Gao, Xiangxian Xu, Ling Liu, Li Liu, Xiang Zhang, Xianxian Liang, Lanqi Cen, Qian Liu, Xiaoli Yuan, Zhenghong Yu

Abstract

Transarterial embolization (TAE) constitutes the gold standard for the treatment of hepatocellular carcinoma. The effect of combination of TAE and peglated-H1/HGFK1 nanoparticles was explored on hepatocellular carcinoma. MTT and Annexin V-FITC were used to determine the cell viability and apoptosis of HepG2, ml-1, LO2, and VX2 cells after the treatment of HGFK1. Next, the orthotopic rabbit was selected to establish the in situ models of VX2 hepatocellular carcinoma. Nanoparticles were synthesized with peglated-PH1 and used to deliver HGFK1 overexpressing plasmids. MRI was performed to monitor tumor volume after being treated with TAE. The protein expression levels of CD31, CD90, and Ki67 were determined by immunohistochemistry. H&E and TUNEL staining were used to determine the necrosis and apoptosis in vivo. HGFK1 significantly inhibited the proliferation and increased the apoptosis of HepG2 and ml-1 cells (P < 0.05). MRI on 14 days after modeling suggested that the tumor showed ring enhancement. MRI on 7 days and 14 days after interventional therapy showed that tumor volume was significantly inhibited after the treatment with TAE and HGFK1 (P < 0.05). The immunohistochemical results 7 days after interventional therapy indicated that the expressions of CD31, CD90, and Ki67 were significantly lower after treatment with TAE and HGFK1 (P < 0.05). TAE and HGFK1 all extended the survival period of rabbits (P < 0.05). PH1/HGFK1 nanoparticle is an innovative and effective embolic agent, which could limit angiogenesis post-TAE treatment. The combination of TAE with PH1/HGFK1 is a promising strategy and might alter the way that surgeons manage hepatocellular carcinoma (HCC).

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