Gold nanoparticle conjugated Rad6 inhibitor induces cell death in triple negative breast cancer cells by inducing mitochondrial dysfunction and PARP-1 hyperactivation: Synthesis and characterization

This study describes the development of a nanotechnology-based vehicle for delivering Rad6-targeting therapy for triple negative breast cancer cells, a breast cancer subtype that currently lacks targeted therapy. SMI#9 is a small molecule inhibitor of Rad6, a central player in DNA damage tolerance or postreplication DNA repair mechanism. To enhance cellular uptake, the parent SMI#9 was chemically modified to enable conjugation via a hydrolysable ester bond to mercaptosuccinic acid-capped gold nanoparticles. SMI#9-GNPs are endocytosed into cells and hydrolyzed intracellularly to release the conjugated drug. The drug released from GNP is therapeutically active in breast cancer cells.108