NiFe-layered double hydroxide nanoparticle for co-delivery of DOX and siRNA to overcome multidrug resistance in MCF-7/ADR cells

Multidrug resistance (MDR) continues to be the major limiting factor in the cure of patients with cancer. Studies have shown that tumor multidrug resistance may be closely related to the multidrug-resistant protein secreted by itself, such as breast cancer resistance protein (BCRP). Therefore, inhibiting the production of multidrug-resistant proteins through genetic intervention may reverse tumor drug resistance. Herein, we use layered double hy-droxide nanoparticles (LDH) to co-deliver DOX and siRNA targeting BCRP RNA to reverse the resistance of MCF-7/ADR cells and enhance the anticancer activity of doxorubicin (DOX). In this platform, DOX is encapsulated in the nanoparticles, which have the characteristics of high drug loading and strong controlled-release, and siRNA is tightly adsorbed on the surface of the nanoparticles through electrostatic action to avoid the degradation of siRNA. Moreover, NiFe-LDH shows excellent ability to deliver siRNA and DOX into cells and enhance the internalization of siRNA and DOX. The experiment further confirms that siRNA-DOX@NiFe-LDH (1:1) shows an effective gene silencing effect and down-regulated the expression of BCRP. In vitro experiments show that siRNA-DOX@NiFe-LDH inhibits cell proliferation by affecting the cell cycle and inducing apoptosis. In vivo experi-ments, MCF-7/ADR xenotransplantation therapy also reveals that siRNA-DOX@NiFe-LDH has a significant antitumor effect. We believe that this work has great potential for reversing the drug resistance of breast cancer and improving the effectiveness of chemotherapy.