血管生成
癌症研究
紫杉醇
细胞毒性
遗传增强
PEDF公司
脐静脉
内皮抑素
细胞凋亡
药理学
生物
癌症
医学
体外
生物化学
内科学
基因
作者
Bei Xu,Quansheng Jin,Jun Zeng,Yasuyuki Takata,Yan Chen,Shuangzhi Li,Daoqiong Gong,Lili He,Xiaoyue Tan,Li Yang,Gu He,Wu Jin,Xiangrong Song
标识
DOI:10.1021/acsami.6b08603
摘要
A rational combination is critical to achieve efficiently synergistic therapeutic efficacy for tumor treatment. Hence, we designed novel antitumor combinations (T-NPs) by integrating the tumor vascular and tumor cells dual-targeting ligand with antiangiogenesis/antitumor agents. The truncated bFGF peptide (tbFGF), which could effectively bind to FGFR1 overexpressed on tumor neovasculature endothelial cells and tumor cells, was selected to modify PLGA nanoparticles (D/P-NPs) simultaneously loaded with PEDF gene and paclitaxel in this study. The obtained T-NPs with better pharmaceutical properties had elevated cytotoxicity and enhanced expression of PEDF and α-tubulin on FGFR1-overexpressing cells. The uptake of T-NPs increased in C26 cells, probably mediated by tbFGF via specific recognization of the overexpressed FGFR1. T-NPs dramatically disrupted the tube formation of primary human umbilical vein endothelial cells (HUVECs) and displayed improved antiangiogenic activity in the transgenic zebrafish model and the alginate-encapsulated tumor cell model. More importantly, T-NPs achieved a markedly higher antitumor efficacy in the C26 tumor-bearing mice model. The antitumor effect involved the inhibition of tumor cell proliferation and angiogenesis, induction of apoptosis, and down-regulation of FGFR1. The enhanced antitumor activity of T-NPs probably resulted from the raised distribution in tumor tissues. In addition, T-NPs had no obvious toxicity as evaluated by weight monitoring, serological/biochemical analyses, and H&E staining. These results revealed that T-NPs, an active targeting gene/chemo-therapy, indeed had superior antitumor efficacy and negligible side effect, suggesting that this novel combination is a potential tumor therapy and a new treatment strategy and that the tbFGF modified nanoparticles could be applied to a wide range of tumor-genetic therapies and/or tumor-chemical therapies.
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