The development of multidrug resistance(MDR)has become an increasingly serious problem in cancer therapy,making the long-term survival of patients with MDRassociated cancers extremely challenging.The cell-membrane overexpression of P-glycoprotein(P-gp),which can actively efflux various anticancer drugs from the cell,is a major mechanism of MDR.Nuclear-uptake nanodrug delivery systems,which enable intranuclear release of anticancer drugs,are expected to address this challenge by by- The development of multidrug resistance (MDR) has become an increasingly serious problem in cancer therapy, making the long-term survival of patients with MDR associated cancers. Extremely challenging. The cell-membrane overexpression of P-glycoprotein (P-gp) efflux various anticancer drugs from the cell, is a major mechanism of MDR. Nuclear-uptake nanodrug delivery systems, which enable intranuclear release of anticancer drugs, are expected to address this challenge by by-