Cytotoxicity of naphthoquinones and their capacity to generate reactive oxygen species is quenched when conjugated with gold nanoparticles

Abstract

Priya Srinivas1,2, Chitta Ranjan Patra2,4, Santanu Bhattacharya2, Debabrata Mukhopadhyay2,31Integrated Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Kerala, India; 2Department of Biochemistry and Molecular Biology; 3Department of Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN, USA; 4Department of Chemical Biology, Indian Institute of Chemical Technology, Hyderabad, IndiaAbstract: Several reports have demonstrated the anticancer activities of plumbagin, a naphthoquinone derivative isolated from plants belonging to Plumbaginaceae family. However, to the best of our knowledge, there are no reports which describe gold nanoconjugation with plumbagin, even though plumbagin is considered to be a promising therapeutic agent. In this report, we demonstrate the fabrication and characterization of gold nanoparticles conjugated with plumbagin (AuPB) that can reduce the toxicity of the latter, and their capacity for cellular localization and generation of reactive oxygen species. The anticancer activity and ability of plumbagin to produce reactive oxygen species was studied and compared with that of bromoderivatives of 1,4 naphthoquinones such as 2-bromo-1,4-naphthoquinone (2-BNQ) and 2,3-dibromo-1, 4-naphthoquinone (2,3-DBNQ) and their gold nanoconjugates. Plumbagin and bromoderivatives of 1,4 naphthoquinones in the form of gold nanoconjugates showed reduced cytotoxicity and apoptosis compared with the pristine compounds, ie, plumbagin, 2-BNQ, and 2,3-DBNQ. Interestingly, we observed that the gold nanoparticles could quench the reactive oxygen species-generating capacity of plumbagin, 2-BNQ, and 2,3-BNQ, which is one of the main mechanisms of action of the naphthoquinones. Therefore, it can be concluded that conjugation with gold nanoparticles can reduce the cytotoxicity of these compounds.Keywords: plumbagin, gold nanoparticles, reactive oxygen species, naphthoquinones, breast cancer