Efficacy of epi-1 modified epirubicin and curcumin encapsulated liposomes targeting-EpCAM in the inhibition of epithelial ovarian cancer cells

Abstract

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.

Keywords:

• Active targeting
• epirubicin
• curcumin
• Epi-1
• angiogenesis
• tumor metastasis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the China Medical Education Association’s ‘Major Scientific Research Projects and Medical Technology Problems in 2020’ program (Grant number: 2020KTS004), the National Natural Science Foundation of China (Grant number: 81874347) and the Liaoning Natural Science Foundation (Grant number: 2019-MS-226).