Enhanced Chemotherapy Efficacy by Sequential Delivery of siRNA and Anticancer Drugs Using PEI-Grafted Graphene Oxide

PEI GO The RNA interference (RNAi) technique, an effective method to inhibit protein expression by targeted cleavage of messenger RNA (mRNA), has made substantial progress since the fi rst demonstration of gene knockdown in mammalian cells. [ 1 ] Short interfering RNA (siRNA) induces specifi c silencing of targeted protein, thus offering signifi cant potential in overcoming multiple drug resistance (MDR) of cancer cells. [ 2 ] For example, Bcl-2 protein, one of the main antiapoptotic defense proteins, is closely related to the MDR of cancer cells. [ 3 ] Knockdown of the Bcl-2 protein expression level in cancer cells by Bcl-2-targeted siRNA would effectively overcome the MDR of cancer cells and sensitize cancer cells to anticancer drugs. [ 3 d, 4 ] Herein, we report sequential delivery of Bcl-2-targeted siRNA and the anticancer drug doxorubicin (DOX) using polyethylenimine (PEI)-functionalized graphene oxide (PEI-GO). We demonstrate that the PEI-GO is an excellent nanocarrier for effective delivery of siRNA and chemical drugs, and that sequential delivery of the siRNA and DOX by PEI-GO into cancer cells exhibits a synergistic effect, which leads to a signifi cantly enhanced chemotherapy effi cacy. To the best of our knowledge, this is the fi rst report on applications of GO-based nanovectors for delivery of siRNA, and sequential delivery of siRNA and anticancer drugs into cancer cells. Graphene, a newly discovered 2D nanomaterial, has been studied extensively due to its fundamental importance and potential applications, [ 5 ] while exploration of its biomedical applications has just started. [ 6 ] Noncovalent adsorption through π – π stacking, electrostatic, and other molecular interactions has proven to be effective for immobilizing chemical drugs, single-stranded DNA, and RNA onto GO sheets. [ 6 a–e]