使用针对-EpCAM的epi-1改良后表阿霉素和姜黄素封装的脂质体,在抑制卵巢上皮癌细胞方面具有良好的疗效。
Efficacy of epi-1 modified epirubicin and curcumin encapsulated liposomes targeting-EpCAM in the inhibition of epithelial ovarian cancer cells.
发表日期:2022 Dec 12
作者:
Yu-Jia Wang, Ling Tang, Xu-Hong Lu, Ji-Tao Liu, Yuan-Yuan Wang, Hong-Xia Geng, Xue-Tao Li, Quan An
来源:
JOURNAL OF LIPOSOME RESEARCH
摘要:
上皮性卵巢癌(EOC)的治疗仍然面临挑战,因为化疗药物的毒性和靶向性不足,以及肿瘤的转移。在这项研究中,我们设计了一种具有纳米结构的靶向脂质体,以克服这些问题。在脂质体中,将表阿霉素和姜黄素封装起来,以实现它们协同的抗肿瘤效果,同时在脂质体表面上修饰了Epi-1以靶向表皮细胞粘附分子(EpCAM)。 Epi-1是一种大环肽,表现出主动靶向增强细胞摄取和对肿瘤细胞的有效细胞毒性。将表阿霉素和姜黄素封装起来,协同抑制新生血管生成和血管样拟态(VM)通道的形成,从而抑制SKOV3细胞的肿瘤转移。含双药的Epi-1脂质体还通过诱导凋亡并下调转移相关蛋白,在体外具有有效的抗肿瘤作用。体内研究表明,含双药的Epi-1脂质体延长了药物在血液中的循环时间,并增加了药物在肿瘤部位的选择性积累。 H&E染色和Ki-67免疫组化也表明,靶向脂质体提高了抗肿瘤活性。此外,靶向脂质体下调了与血管生成有关的蛋白,抑制了血管生成和肿瘤转移。总之,生产含双药的Epi-1脂质体是治疗EOC的有效策略。
Treatment of epithelial ovarian cancer (EOC) is a challenge because it still leads to unsatisfactory clinical prognosis. This is due to the toxicity and poor targeting of chemotherapeutic agents, as well as metastasis of the tumor. In this study, we designed a targeted liposome with nanostructures to overcome these problems. In the liposomes, epirubicin and curcumin were encapsulated to achieve their synergistic antitumor efficacy, while Epi-1 was modified on the liposomal surface to target epithelial cell adhesion molecule (EpCAM). Epi-1, a macrocyclic peptide, exhibits active targeting for enhanced cellular uptake and potent cytotoxicity against tumor cells. The encapsulation of epirubicin and curcumin synergistically inhibited the formation of neovascularization and vasculogenic mimicry (VM) channels, thereby suppressing tumor metastasis on SKOV3 cells. The dual drug loaded Epi-1-liposomes also induced apoptosis and downregulated metastasis-related proteins for effective antitumor in vitro. In vivo studies showed that dual drug loaded Epi-1-liposomes prolonged circulation time in the blood and increased the selective accumulation of drug at the tumor site. H&E staining and immunohistochemistry with Ki-67 also showed that targeted liposomes elevated antitumor activity. Also, targeted liposomes downregulated angiogenesis-related proteins to inhibit angiogenesis and thus tumor metastasis. In conclusion, the production of dual drug loaded Epi-1-liposomes is an effective strategy for the treatment of EOC.