Folic acid modified copper oxide nanoparticles for targeted delivery in in vitro and in vivo systems
Abstract
Copper oxide nanoparticles are known to exhibit toxic effects on a variety of cell types. In the present study, copper oxide nanoparticles were modified with folic acid for targeted delivery. The physicochemical properties of copper oxide nanoparticles (CuO NPs) and folic acid conjugated copper oxide nanoparticles (CuO–FA NPs) were studied by Dynamic light scattering (DLS), Field emission scanning electron microscopy (FE-SEM) and Fourier transform infrared spectroscopy (FTIR). To determine targeting efficacy, we have used folate receptor positive and folate receptor knock down human breast cancer cells MCF7. Flow cytometric analysis, generation of ROS and expression of apoptotic proteins (cleaved PARP, decreased p-BAD) indicated that most cell death occurred through apoptosis in CuO–FA NPs treated MCF7 cells. In the in vivo study, we used Dalton's lymphoma (DL) cell induced tumor in mice. We successfully delivered CuO and CuO–FA NPs through peritoneal injection after induction of the tumor. Reactive oxygen species (ROS), glutathione (GSH) was measured in DL cells isolated from tumor bearing mice. All of these data indicated that CuO–FA NPs was more effective in killing the tumor cells and successful reduction of the tumor was observed in CuO–FA NPs treated mice after 15 days of treatment. These findings have important implications for understanding the potential anticancer properties induced by folic acid modified CuO NPs.