A novel drug “copper acetylacetonate” loaded in folic acid-tagged chitosan nanoparticle for efficient cancer cell targeting

Abstract

Several copper compounds have proven anti-cancer activity. Similarly, curcumin a derivative of 1,3 diketone, which is not plenty in nature, has comparable anti-cancer activity. In this work, we have explored the synergistic anti-cancer activity of copper ion and acetylacetone complex containing 1,3 diketone group. The cytotoxicity of the copper acetylacetonate (CuAA) complex was evaluated on various cancer cells and LD₅₀ doses were determined. To investigate the mechanism, various biochemical assays were performed and reactive oxygen species as well as the glutathione level in the cell were found to be increased after the treatment with the above-mentioned complex. Further this reagent induced apoptosis and reduced mitochondrial membrane potential of the cells. Because of the poor solubility and reasonable cytotoxicity of CuAA, polymer nanoparticles (NPs) of chitosan derivatives were used for delivery in cancer cells. For the targeted delivery, folic acid-tagged hydrophobic-modified chitosan NPs were developed and the CuAA was encapsulated. Finally, these drug-encapsulated NPs were successfully delivered to folate receptor over-expressed cancer cells. Thus using nanotechnology, we developed an anti-cancer agent suitable for targeted delivery.

• Cancer targeting
• chitosan
• folate
• nanoparticles

Acknowledgements

The authors would like to thank Dr Mamta Chawla Sarkar, Mr George Banik of NICED (National Institute of Cholera and Enteric Diseases), Kolkata for helping us with FACS instrumentation, Dr Amar Nath Ghosh of NICED, Kolkata for Transmission Electron Microscopic facility and Dr Debajyoti Ghoshal of Jadavpur University, Kolkata for Fourier transform infrared spectroscopy.