The discovery of cancer stem cells (CSCs) has changed the applicability of chemotherapy[1].CSCs evade the anti-cancer effects of standard chemotherapy on a tumor and have emerged as an underestimated biological barrier to the success of systemic chemotherapy.The protein ABCG2 is highly expressed in drug-resistant cancer cells and CSCs and largely contributes to their drug resistance[2].Here we constructed bioresponsive functionalized mesoporous silica nanoparticles (MSNs) for co-delivery of doxorubicin (Dox) and shABCG2 into CSCs in vitro and in vivo (Fig.1).