About the Cover
Cover image

ABOUT THE COVER
The yeast RAD6 homologues HHR6A (a.k.a. RAD6A or UBE2A) and HHR6B (a.k.a. RAD6B or UBE2B) encode ubiquitin conjugating enzymes or E2s that play a central role in translesion DNA synthesis (TLS), damage-induced mutagenesis and proteolysis. Consistent with RAD6 function, treatment of breast cancer cells with a RAD6-selective small molecule inhibitor SMI#9 restores chemosensitivity by inhibition of TLS. Delivery of SMI#9 is challenging due to its poor aqueous solubility. Saadat and colleagues synthesized SMI#9 as a prodrug-gold nanoparticle (GNP) conjugate to overcome its solubility limitations and to effectively deliver therapeutic SMI#9 to triple negative breast cancers (TNBCs). As depicted on the cover, both blank and SMI#9 conjugated GNPs are endocytosed into the TNBC cells but cell death is only induced by SMI#9-GNP as detected by acridine orange/ethidium bromide staining. GNPs delivering SMI#9 prodrug exhibited improved in vivo pharmacokinetics and inhibited TNBC growth in vivo.
The GNP platform allows for SMI#9 conjugation and delivery to treat TNBCs, a breast cancer subtype with poor prognosis and lacking targeted therapies.