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Enhanced antitumor efficacy of functionalized doxorubicin plus schisandrin B co-delivery liposomes via inhibiting epithelial-mesenchymal transition
Journal of Liposome Research ( IF 3.6 ) Pub Date : 2020-04-13 , DOI: 10.1080/08982104.2020.1745831
Fu-Yi Cai 1 , Xue-Min Yao 1 , Ming Jing 1 , Liang Kong 1 , Jing-Jing Liu 1 , Min Fu 1 , Xin-Ze Liu 1 , Lu Zhang 1 , Si-Yu He 1 , Xue-Tao Li 1 , Rui-Jun Ju 2
Affiliation  

Non-small cell lung cancer (NSCLC) is a malignant cancer characterized by easy invasion, metastasis and poor prognosis, so that conventional chemotherapy can't inhibit its invasion and metastasis. Doxorubicin, as a broad-spectrum antitumor drug, cannot be widely used in clinic because of its poor targeting, short half-life, strong toxicity and side effects. Therefore, the aim of our study is to construct a kind of PFV modified doxorubicin plus schisandrin B liposomes to solve the above problems, and to explore its potential mechanism of inhibiting NSCLC invasion and metastasis. The antitumor efficiency of the targeting liposomes was carried out by cytotoxicity, heating ablation, wound healing, transwell, vasculogenic mimicry (VM) channels formation and metastasis-related protein tests in vitro. Pharmacodynamics were evaluated by tumor inhibition rate, HE staining and TUNEL test in vivo. The enhanced anti-metastatic mechanism of the targeting liposomes was attributed to the down-regulation of vimentin, vascular endothelial growth factor (VEGF), matrix metalloproteinase 9 (MMP-9) and up-regulation of E-cadherin. In conclusion, the PFV modified doxorubicin plus schisandrin B liposomes prepared in this study provided a treatment strategy with high efficiency for NSCLC.

中文翻译:

功能化多柔比星联合五味子乙素共递送脂质体通过抑制上皮-间质转化增强抗肿瘤功效

非小细胞肺癌(non-small cell lung cancer, NSCLC)是一种以易侵袭、易转移、预后差为特征的恶性肿瘤,常规化疗无法抑制其侵袭转移。阿霉素作为一种广谱抗肿瘤药物,由于靶向性差、半衰期短、毒副作用大,不能广泛应用于临床。因此,本研究旨在构建一种PFV修饰的多柔比星+五味子乙素脂质体以解决上述问题,并探讨其抑制NSCLC侵袭转移的潜在机制。靶向脂质体的抗肿瘤效率通过体外细胞毒性、加热消融、伤口愈合、transwell、血管生成模拟 (VM) 通道形成和转移相关蛋白测试来进行。通过体内抑瘤率、HE染色和TUNEL试验评价药效学。靶向脂质体增强的抗转移机制归因于波形蛋白、血管内皮生长因子(VEGF)、基质金属蛋白酶9(MMP-9)的下调和E-钙粘蛋白的上调。综上所述,本研究制备的PFV修饰的多柔比星加五味子B脂质体为NSCLC提供了一种高效的治疗策略。
更新日期:2020-04-13
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