Background: Ovarian cancer is a leading cause of death in gynecologic malignancies. The high mortality is mainly caused by advanced stage at presentation in most patients. Even after the combination of cytoreductive surgery and systemic platinum and taxane treatment, most patients relapse and eventually succumb to the disease. Therefore, there is an urgent need for new treatments. 
Purpose: A novel folate (FA)-targeted co-delivery of docetaxel (DTX) and gemcitabine (GEM) nanoparticles (NPs) was developed to overcome ovarian cancer. 
Materials and methods: Physicochemical characteristics of NPs such as size, morphology, and release profiles were explored. In vitro and in vivo studies were carried out to assess the efficacy of their antitumor activity in target cells. 
Results: FA modified DTX and GEM co-loaded NPs were prepared using the solvent evaporation method. The NPs with a particle size of ∼120nm were stable in the observation period. The hemolysis results indicated that FA-PEG₂₀₀₀-PLGA was potentially feasible for targeted antitumor drug delivery through blood circulation. In vitro release study suggested that in comparison with the free drug, PLGA-DTX/GEM NPs and FA-PEG₂₀₀₀-PLGA-DTX/GEM NPs had sustained-release properties. However, there was no obvious difference between the two NPs with the same drug in the release profile. Ovarian cancer cells in vitro efficiently took up the non-targeted and FA-targeted NPs; improved cytotoxicity was observed in the FA-targeted NPs, showing a 3.59- fold drop in the IC₅₀ in SKOV-3 cells as compared to DTX/GEM alone. Cellular uptake showed that through surface modification, more drugs entered the cell successfully. Pharmacodynamics results showed a statistically significant effect on the rate of reduction of tumor volume for FA-PEG₂₀₀₀-PLGA-DTX/GEM NPs than other groups and no toxicity of organs.
Conclusion: The present study indicates that the FA-PEG₂₀₀₀-PLGA-DTX/GEM NPs provides a promising platform for the treatment of ovarian cancer.
Keywords: folate, co-delivery, docetaxel, gemcitabine, nanoparticles