Preclinical Evaluation to Specifically Target Ovarian Cancer with Folic Acid-Conjugated Nanoceria.

摘要

Despite the fact that there have been significant developments in anti-cancer technology, ovarian cancer still remains one of the leading causes of gynecological cancer deaths in the United States. To contribute towards novel approaches with minimal toxicity in treatment of ovarian cancer we proposed the present work, where we are integrating the field of nanotechnology with ovarian cancer cell s unique property of overexpressing folic acid receptor alpha (FR-a) to specifically target ovarian cancer. A cerium oxide nanoparticle, called Nanoceria (NCe), that has the ability to act as an anti- oxidant in similar capacity as biological anti-oxidants was selected. NCe in our hands exhibited efficacy in inhibiting ovarian tumor growth in vivo. Taking advantage of the nanotechnology, NCe was conjugated with molecules of folic acid to specifically target ovarian tumors as they are known to over-express folate receptor. This would result in specific killing of ovarian cells by NCe while minimizing toxicity to normal tissue. Dr Seal s laboratory (UCF) was able to successfully conjugate NCe to folic acid to prepare folic acid tagged Nanoceria called FA-NCe. FA-NCe was tested in vitro and was observed to have higher anti-growth activity against ovarian cancer cells. When given in animals, FA-NCe was more potent in inhibiting ovarian tumor growth than NCe alone and enhanced the cytotoxicity of cisplatin in vivo.