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

Abstract
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.
AuthorsMiaojuan Qiu, Junzong Chen, Xiuyu Huang, Binbin Li, Shiqiang Zhang, Peng Liu, Qiang Wang, Zhi Rong Qian, Yihang Pan, Yu Chen, Jing Zhao
JournalACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 14 Issue 19 Pg. 21954-21965 (May 18 2022) ISSN: 1944-8252 [Electronic] United States
PMID35508299 (Publication Type: Journal Article)
Chemical References
  • Calcium Phosphates
  • Oligopeptides
  • Phosphates
  • Doxorubicin
  • Calcium
Topics
  • Animals
  • Calcium
  • Calcium Phosphates (therapeutic use)
  • Cell Line, Tumor
  • Doxorubicin (pharmacology, therapeutic use)
  • Female
  • Humans
  • Mice
  • Nanoparticles
  • Oligopeptides (pharmacology, therapeutic use)
  • Ovarian Neoplasms (drug therapy)
  • Phosphates

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