Ling Tang,1 Yu-Jia Wang,2 Yuan-Yuan Wang,2 Shu-Tong Li,3 Liang Kong,3 Xue-Tao Li,3 Ling-Ling Ma,1 Xiu-Xiu Liu1 

1Department of Obstetrics and Gynecology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 2Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 3School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, 116600, People’s Republic of China

Correspondence: Ling-Ling Ma; Xiu-Xiu Liu, Department of Obstetrics and Gynecology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China, Email 826269013@qq.com; 1225949002@qq.com

Purpose: Ovarian cancer is a fatal gynecologic malignancy with a high rate of abdominal metastasis. Chemotherapy still has a poor clinical prognosis for ovarian cancer patients, with cell proliferation and angiogenesis leading to invasion, migration, and recurrence. To overcome these obstacles, we constructed a novel HA-modified paclitaxel and diosgenin liposome (PEG-TK-HA-PDLPs) using two novel functional materials, DSPE-PEG2000-HA and DSPE-PEG2000-TK-PEG5000, to specifically deliver the drugs to the tumor site in order to reduce OC cell proliferation and anti-angiogenic generation, thereby inhibiting invasion and migration.
Methods and Results: PEG-TK-HA-PDLPs were prepared by film dispersion, with ideal physicochemical properties and exhibits active targeting for enhanced cellular uptake. The ZIP synergy score for PTX and Dios was calculated using the online SynergyFinder software to be 3.15, indicating synergy. In vitro results showed that PEG-TK-HA-PDLPs were highly cytotoxic to ID8 cells, induced ID8 cell apoptosis, and inhibited ID8 cell migration and invasion. In vivo studies showed that PEG-TK-HA-PDLPs could prolong the circulation time in the blood, accumulate significantly in the tumor site, and effectively fight against angiogenesis with significant anti-tumor effects.
Conclusion: The production of PEG-TK-HA-PDLPs is an effective strategy for the treatment of OC.

Keywords: ovarian cancer, functional liposomes, paclitaxel, diosgenin, ROS-response, HA