Self-Assembled Graphene oxide Nanoparticles for Damaging DNA in Cancer Cells

Abstract

Cancer is a multifactorial mutagenic disease making it one of the leading causes of death globally. The complexity and heterogeneity associated with cancer presents a challenging problem with respect to its treatment. In recent years, the incorporation of nanotechnology in cancer treatment has revolutionized the field of cancer therapy. Various nanoplatforms have been used for anticancer drugs to specifically target cancer cells, but all have their own associated drawbacks limiting their application. Also, the combined use of multiple drugs into a single nanoplatform still remains a considerable challenge. Graphene oxide-based biocompatible nanoscale materials, by virtue of their unique physicochemical properties and the large surface have the potential to tackle this complication. To address this issue, we have developed novel cisplatin-mediated self-assembled 3D graphene oxide spherical nanoparticles (GO-NP’s) of size less than 200nm from 2D graphene oxide sheets. The nanoparticles can also be loaded with additional DNA damaging drugs along with cisplatin-which is a widely used drug in cancer treatment. These dual drug-containing graphene oxide spherical nanoparticles successfully displayed their anticancer activity by damaging the DNA which is the most important target to cease essential cellular functions and hence induce apoptosis in cancer cells. Further, to enhance the dispersibility and biocompatibility of the 3D GO-NP’s for safer biomedical applications, we employed surface functionalization of the graphene oxide sheets with biocompatible polymers like Polyethyleneglycol (PEG) and Poly-maleic acid (PMA) and self-assembled them into spherical nanoparticles via cisplatin. Subsequently, we loaded the nanoparticles with an inhibitor of an important DNA-associated enzyme, Topoisomerase I. The modified nanoparticles induced DNA damage along with enzyme inhibition, activating programmed cell death in HeLa cervical cancer cells. Lastly, we have engineered a lipid-coated self-assembled spherical 3D-GO nanoparticle (GO-Nanocell), which can concomitantly load and release multiple drugs: t opoisomerase I and II inhibitors along with cisplatin. The GO-Nanocells simultaneously induced DNA damage along with Topoisomerase (TOP I and TOP II) poisoning, triggering apoptosis in HeLa cells. The graphene oxide based approaches presented here can serve as a tool to impair multiple targets inside the cancer cells in a synchronized manner for better therapeutic effect in future cancer therapy.