Ultrasound Mediated Drug-Loaded Nanoparticles Crossing Cell Membranes as a New Strategy to Reverse Cancer Multidrug Resistance

Abstract

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.

Study of the mechanisms underlying the reversal of multidrug resistance of human neuroblastoma multidrug-resistant cell line SK-N-SH/MDR1 by low-intensity pulsed ultrasound

“…According to previous reports (31)(32)(33)(34), LIPUS may also strengthen the transport of genes, proteins, and drugs to target organ tissues and cells, consequently improving their therapeutic effects. LIPUS may therefore become an important therapeutic modality in the future.…”

Daunorubicin-TiO2 nanocomposites as a “smart” pH-responsive drug delivery system

“…In addition, DNR, which is positively charged, can be easily self-assembled onto the surface of TiO 2 nanoparticles through electrostatic interaction as the relative surface of TiO 2 nanoparticles is negatively charged in pH 7.4 aqueous solutions. 8,10 Thus, the authors believe that DNR was absorbed onto the TiO 2 nanoparticles by forming complexes with transition metal titanium and by electrostatic interaction. Figure 2 shows a proposed schematic representation of DNR loading onto TiO 2 nanoparticles through the formation of DNR-TiO 2 nanocomposites as a DDS.…”

“…When treated by TiO 2 nanoparticles, about 95% of the cells survived ( Figure 5, blue line), which is consistent with a previous report. 10 The lack of cytotoxicity of TiO 2 nanoparticles thus ensures a wide potential range of applications in the field of biomedical science and cancer therapy. of DNR, lethality increased, suggesting a dose-dependent effect in vitro.…”

Anticancer efficacy enhancement and attenuation of side effects of doxorubicin with titanium dioxide nanoparticles

“…When treated by TiO 2 nanoparticles (10 µg/mL ), about 95% of the cells survived ( Figure 4, red line), which is consistent with our previous report. 15 This result suggests lack of cytotoxicity for TiO 2 nanoparticles, thus ensuring a wide potential range of applications in the field of biomedical science and cancer therapy. Compared with doxorubicin alone (Figure 4, pink line), the viability of SMMC-7721 cells treated by DOX-TiO 2 nanocomposites markedly decreased (Figure 4, blue line).…”

“…3,4 A variety of organic 5,6 and inorganic [7][8][9][10] biomaterials have been explored for drug delivery purposes, among which the semiconductor nanomaterials, such as titanium dioxide (TiO 2 ) nanoparticles and zinc oxide nanorods, are attracting an increasing level of attention. [11][12][13][14][15] Barick et al reported a method for entrapping drugs at sites capable of complexing with transition metal ions and suggested that drug release is dependent on the pH of the medium and the nature of the materials which encapsulate the drug. 12 It is also suggested that this general strategy could be readily extended to other inorganic carriers.…”