Dihydroartemisinin and transferrin dual-dressed nano-graphene oxide for a pH-triggered chemotherapy.

Abstract Dihydroartemisinin (DHA) is a unique anti-malarial drug isolated from the plant Artemisia annua. Recently, it has been studied as an alternative modality for cancer therapy, utilizing its reactive oxygen species (ROS) yielding mechanism from interacting with Ferrous ion (Fe (Ⅱ)). In this work, a novel nanodrug (DHA-GO-Tf) is constructed based on nanoscale Graphene oxide (GO) dual-dressed with DHA and Transferrin (Tf). Tf dually functions as a pilot for the nanoparticle to target tumor cell with over expressed Transferrin receptor (TfR) and a ferric ion carrier. Upon tumor cellular endocytosis, Ferric ion (Fe(Ⅲ)) is released from the Tf, triggered by the low pH in the lysosomes of the tumor cell. The intracellular Fe (Ⅲ) is reduced to Fe (Ⅱ) and interacts with DHA to increase its cytotoxicity. The potential of this alternative anti-tumor modality is demonstrated both in vitro and in vivo . Comparing with DHA alone, the nanodrug DHA-GO-Tf resulted in a significantly enhanced tumor delivery specificity and cytotoxicity, and achieved a complete tumor cure in mice with minimal side-effects.