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聚阳离子脂质体包裹的磷酸钙纳米颗粒递送的VEGF siRNA用于抑制乳腺癌肿瘤血管生成

VEGF siRNA delivered by polycation liposome-encapsulated calcium phosphate nanoparticles for tumor angiogenesis inhibition in breast cancer.

作者信息

Chen Jinliang, Sun Xiaoyi, Shao Rong, Xu Yichao, Gao Jianqing, Liang Wenquan

机构信息

Center of Clinical Pharmacology, The Second Affiliated Hospital of Zhejiang University, School of Medicine.

Department of Pharmacy, Zhejiang University City College.

出版信息

Int J Nanomedicine. 2017 Aug 21;12:6075-6088. doi: 10.2147/IJN.S142739. eCollection 2017.

DOI:10.2147/IJN.S142739
PMID:28860767
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5573052/
Abstract

Angiogenesis plays an important role in tumor development and metastasis, and many cancer cells upregulate VEGF expression to promote angiogenesis. Silencing VEGF expression by RNA interference is expected to be a promising strategy to suppress the tumor growth. However, low transfection efficiency and instability are the main barriers for small interfering RNA (siRNA) delivery. In this study, we developed polycation liposome-encapsulated calcium phosphate nanoparticles (PLCP) for siRNA delivery in vivo. VEGF expression silencing effect in MCF-7 cells was investigated by real-time quantitative polymerase chain reaction and Western blot assay. VEGF siRNA mediated by PLCP can reduce 60%-80% VEGF expression in vitro, which was significantly higher than that mediated by Lipofectamine 2000. Furthermore, significant tumor growth and angiogenesis inhibition were observed in MCF-7 xenografts mice when treated with PLCP/VEGF siRNA or combined with doxorubicin. In conclusion, the combination of silencing VEGF expression and chemotherapeutics would be a potential treatment for cancer therapy.

摘要

血管生成在肿瘤发展和转移中起重要作用，许多癌细胞上调血管内皮生长因子（VEGF）表达以促进血管生成。通过RNA干扰沉默VEGF表达有望成为抑制肿瘤生长的一种有前景的策略。然而，低转染效率和不稳定性是小干扰RNA（siRNA）递送的主要障碍。在本研究中，我们开发了用于体内siRNA递送的聚阳离子脂质体包裹的磷酸钙纳米颗粒（PLCP）。通过实时定量聚合酶链反应和蛋白质免疫印迹分析研究了MCF-7细胞中VEGF表达沉默效果。PLCP介导的VEGF siRNA在体外可降低60%-80%的VEGF表达，这显著高于脂质体2000介导的效果。此外，在用PLCP/VEGF siRNA处理或与阿霉素联合处理的MCF-7异种移植小鼠中观察到显著的肿瘤生长抑制和血管生成抑制。总之，沉默VEGF表达与化疗药物联合使用将是癌症治疗的一种潜在疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ebd/5573052/9db0e3695c16/ijn-12-6075Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ebd/5573052/a62a1af57550/ijn-12-6075Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ebd/5573052/672bf2c41c4d/ijn-12-6075Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ebd/5573052/2a6f53e73dcf/ijn-12-6075Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ebd/5573052/a1bc919f7972/ijn-12-6075Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ebd/5573052/9db0e3695c16/ijn-12-6075Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ebd/5573052/a62a1af57550/ijn-12-6075Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ebd/5573052/672bf2c41c4d/ijn-12-6075Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ebd/5573052/2a6f53e73dcf/ijn-12-6075Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ebd/5573052/a1bc919f7972/ijn-12-6075Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ebd/5573052/9db0e3695c16/ijn-12-6075Fig5.jpg

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