Antitumor effects of brucine immuno-nanoparticles on hepatocellular carcinoma in vivo

Qin,Jianmin; Yang,Lin; Sheng,Xia; Sa,Zhongqiu; Huang,Tao; Li,Qi; Gao,Kepan; Chen,Qinghua; Ma,Jingwei; Shen,Hebai

doi:10.3892/ol.2018.8168

Antitumor effects of brucine immuno-nanoparticles on hepatocellular carcinoma in vivo

Authors:
- Jianmin Qin
- Lin Yang
- Xia Sheng
- Zhongqiu Sa
- Tao Huang
- Qi Li
- Kepan Gao
- Qinghua Chen
- Jingwei Ma
- Hebai Shen
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Affiliations: Department of General Surgery, The Third Hospital, The Second Military Medical University, Shanghai 201805, P.R. China, Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China, National Pharmaceutical Engineering Research Center, Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, P.R. China, Department of Physical Chemistry, Shanghai Normal University, Shanghai 200234, P.R. China
Published online on: March 2, 2018 https://doi.org/10.3892/ol.2018.8168
Pages: 6137-6146
Copyright: © Qin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In vitro and in vivo studies have demonstrated that brucine is able to inhibit the proliferation of liver cancer cells and growth of animal tumors, and may be a promising anticancer drug. However, high toxicity, poor water solubility, short half‑life, narrow therapeutic window, and similar therapeutic and toxic doses limit its clinical application in the treatment of malignant tumors. In our previous study, brucine immuno‑nanoparticles were successfully prepared and added to the culture medium of liver cancer SMMC‑7721 cells, and the results indicated that the brucine immuno‑nanoparticles were able to target the cell membrane of liver cancer SMMC‑7721 cells and significantly inhibit the proliferation, adhesion, invasion and metastasis of SMMC‑7721 cells. The aim of the present study was to investigate the antitumor effect of brucine immuno‑nanoparticles in vivo by establishing an in situ transplanted liver cancer in nude mice. The results indicated that in vivo application of the brucine immuno‑nanoparticles resulted in temporary liver and kidney damage, and significantly reduced the α‑fetoprotein (AFP) secretion of tumor cells (Bru‑NP‑MAb vs. the other groups; P<0.05). The brucine concentration of tumor tissues in the brucine immuno‑nanoparticles group was significantly increased compared with that of the brucine nanoparticles group (Bru‑NP‑MAb vs. Bru‑NP group or brucine group; P<0.05). The brucine immuno‑nanoparticles were able to inhibit tumor growth and cluster of differentiation 34 expression and angiogenesis of tumor tissues, and induce the apoptosis of tumor cells (Bru‑NP‑MAb vs. Bru‑NP group or brucine group; P<0.05). In conclusion, as a novel type of targeted drug, brucine nanoparticles combined with anti‑AFP monoclonal antibodies was more effective compared with brucine nanoparticles or brucine alone in inhibiting tumor growth via the enhancement of apoptosis, and the suppression of proliferation and angiogenesis in vivo. Therefore, the brucine immuno‑nanoparticle is a promising targeted drug for the treatment of hepatocellular carcinoma.

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