Engineering Chemotherapeutic-Augmented Calcium Phosphate Nanoparticles for Treatment of Intraperitoneal Disseminated Ovarian Cancer

Yu Chen · 2022-05-04

Ovarian cancer is a common gynecologic malignancy with a high fatality rate. Intraperitoneal chemotherapy has been proved as an efficient clinical treatment for disseminated ovarian cancer. However, there are limitations for conventional small molecule drugs to achieve an ideal therapeutic effect. Herein, a synergistic treatment for intraperitoneally disseminated ovarian cancer was achieved by Arg-Gly-Asp (RGD)-modified amorphous calcium phosphate loading with doxorubicin (designated as RGD-CaPO/DOX). The engineered calcium-involved nanomedicine augmented the therapeutic effect of DOX by aggravating endoplasmic reticulum stress, calcium overload, and mitochondrial dysfunction, ultimately triggering mitochondrial apoptosis in the SKOV3 (human ovarian cancer) cell line. In an intraperitoneally disseminated tumor model, RGD modification and the weak negative surface potential of the NPs were beneficial for intraperitoneal retention and tumor targeting. Moreover, intraperitoneal injection of RGD-CaPO/DOX NPs resulted in a favorable antitumor effect. The mean survival time of SKOV3-bearing mice was significantly extended from 29 to 59 days with negligible toxicity. Therefore, this study has been designed to provide an effective chemotherapeutic-augmented treatment for intraperitoneally disseminated ovarian cancer.
Authors
Funding

Sun Yat-sen University

ZSQYBRJH0001

Ministry of Science and Technology of the People's Republic of China

2018YFA0902801

Science, Technology and Innovation Commission of Shenzhen Municipality

JCYJ20190809150409433

Science, Technology and Innovation Commission of Shenzhen Municipality

JCYJ20210324122612032

Science, Technology and Innovation Commission of Shenzhen Municipality

SGLH20181109105202075

Shanghai Municipal People's Government

21JC1406002

National Natural Science Foundation of China

81872441

National Natural Science Foundation of China

81902426

Chinese Academy of Sciences

GJHZ2072

Shanghai Science and Technology Program

21010500100

Guangdong Provincial Key Laboratory of Digestive Cancer Research, Seventh Affiliated Hospital, Sun Yat-sen University

2021B1212040006