Co-Loaded Reversal Agent and Chemotherapeutic Nanoerythrosomes to Overcome Cancer Multidrug Resistance

The multidrug resistance (MDR) is still a major obstacle in cancer chemotherapeutic treatments. The purpose of this study is to challenge the MDR in tumors by using nanoerythrosomes (NEs) co-loaded P-glycoprotein (P-gp) inhibitor and a chemotherapeutic agent. Nanoerythrosomes were prepared by extrusion, in which the red blood cells (erythrocytes) ghost suspension is extruded through a polycarbonate membrane filter pore by 8-10 consecutive extrusions in an extrusion device. Then verapamil (Ver) and doxorubicin (Dox) were co-loaded into NEs with a hypotonic dialysis method (denoted as Ver/Dox/ NEs), which acted as a drug delivery system. The multidrug resistant leukemia K562/A02 cells were treated with the denoted Ver/Dox/ NEs. In vitro and in vivo, the reversal effect on MDR in human leukemic cells were evaluated by flow cytometer, Cell Counting Kit-8 assays, and Western blot analysis. Results demonstrated that Ver/Dox/NEs could inhibit the function of P-glycoprotein by Ver as reversal agent, significantly increase the uptake of Dox, enhance the sensitivity of the MDR cancer cells to the chemotherapeutic agent, and induce apoptosis while avoiding the toxic side effects. It was therefore concluded that Ver/Dox/ NEs could represent a promising approach in overcoming tumor MDR.