Folic acid tagged nanoceria as a novel therapeutic agent in ovarian cancer

BMC Cancer

Research Article

Ankur Gupta¹  Soumen Das¹  Sudipta Seal²  Shailendra Giri³  Calvin Tebbe⁴  Jasdeep Chhina⁴  Miriana Hijaz⁴  Zaid Al-Wahab⁴  Sajad Dar⁴  Adnan Munkarah⁵  Ramandeep Rattan⁵  Ismail Mert⁶ 

[1] Advanced Materials Processing and Analysis Center, Nanoscience and Technology Center, Materials Science and Engineering, University of Central Florida, Orlando, FL, USA;Advanced Materials Processing and Analysis Center, Nanoscience and Technology Center, Materials Science and Engineering, University of Central Florida, Orlando, FL, USA;College of Medicine, University of Central Florida, Orlando, FL, USA;Department of Neurology, Henry Ford Hospital, Detroit, MI, USA;Josephine Ford Cancer Institute, Henry Ford Hospital, Detroit, MI, USA;Division of Gynecology Oncology, Department of Women’s Health, Henry Ford Hospital, Detroit, MI, USA;Division of Gynecology Oncology, Department of Women’s Health, Henry Ford Hospital, Detroit, MI, USA;Josephine Ford Cancer Institute, Henry Ford Hospital, Detroit, MI, USA;Division of Gynecology Oncology, Department of Women’s Health, Henry Ford Hospital, Detroit, MI, USA;Wayne State University, Detroit, MI, USA;

关键词: Folic acid conjugated nanoceria;    Ovarian cancer;    Nano cerium oxide;    A2780;    Targeted therapy;   

DOI  :  10.1186/s12885-016-2206-4

 received in 2015-07-31, accepted in 2016-02-20,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundNanomedicine is a very promising field and nanomedical drugs have recently been used as therapeutic agents against cancer. In a previous study, we showed that Nanoceria (NCe), nanoparticles of cerium oxide, significantly inhibited production of reactive oxygen species, cell migration and invasion of ovarian cancer cells in vitro, without affecting cell proliferation and significantly reduced tumor growth in an ovarian cancer xenograft nude model. Increased expression of folate receptor-α, an isoform of membrane-bound folate receptors, has been described in ovarian cancer. To enable NCe to specifically target ovarian cancer cells, we conjugated nanoceria to folic acid (NCe-FA). Our aim was to investigate the pre-clinical efficacy of NCe-FA alone and in combination with Cisplatin.MethodsOvarian cancer cell lines were treated with NCe or NCe-FA. Cell viability was assessed by MTT and colony forming units. In vivo studies were carried in A2780 generated mouse xenografts treated with 0.1 mg/Kg NCe, 0.1 mg/Kg; NCe-FA and cisplatinum, 4 mg/Kg by intra-peritoneal injections. Tumor weights and burden scores were determined. Immunohistochemistry and toxicity assays were used to evaluate treatment effects.ResultsWe show that folic acid conjugation of NCe increased the cellular NCe internalization and inhibited cell proliferation. Mice treated with NCe-FA had a lower tumor burden compared to NCe, without any vital organ toxicity. Combination of NCe-FA with cisplatinum decreased the tumor burden more significantly. Moreover, NCe-FA was also effective in reducing proliferation and angiogenesis in the xenograft mouse model.ConclusionThus, specific targeting of ovarian cancer cells by NCe-FA holds great potential as an effective therapeutic alone or in combination with standard chemotherapy.

【 授权许可】

CC BY   
© Hijaz et al. 2016