Ultrasound mediated drug-loaded nanoparticles crossing cell membranes as a new strategy to reverse cancer multidrug resistance.

The emergence of the multidrug resistance (MDR) phenomenon in tumor has rendered many currently available chemotherapeutic drugs ineffective. Although many strategies have been explored to overcome MDR, the results have been disappointing to the obstacle. The aim of this study was to investigate whether the new strategy of combining drug-loaded nanoparticles (Nps) and ultrasound (US) would show useful effects on the reversal of MDR in tumor. The MDR leukemia K562/A02 cells were treated with the daunorubicin (DNR)-loaded TiO2 Nps drug carrier and US exposure. We observed good biocompatibility of the therapeutic approach, and the fresh evidence from the electrochemical studies, MTT assays, and caspase-3 immunocytochemistry demonstrated that the strategy could significantly increase the uptake of DNR by drug-resistant leukemia cells, and enhance the sensitivity of the MDR cells to the chemotherapeutic agents after released in the cells. The resisting fold became obviously lower and the apoptosis was induced in the cells as well. It was therefore concluded that the strategy could have good reversal ability of MDR in tumor. These findings reveal that the reversal of MDR in tumor by US mediated drug-loaded Nps crossing cell membranes could represent promising approach in cancer therapy.