Altering the response of intracellular reactive oxygen to magnetic nanoparticles using ultrasound and microbubbles

Abstract

Engineered iron oxide magnetic nanoparticles (MNPs) are one of the most promising tools in nanomedicine-based diagnostics and therapy. However, increasing evidence suggests that their specific delivery efficiency and potential long-term cytotoxicity remain a great concern. In this study, using 12 nm γ-Fe2O3 MNPs, we investigated three types of uptake pathways for MNPs into HepG2 cells: (1) a conventional incubation endocytic pathway; (2) MNPs co-administrated with microbubbles under ultrasound exposure; and (3) ultrasound delivery of MNPs covalently coated on the surface of microbubbles. The delivery efficiency and intracellular distribution of MNPs were evaluated, and the cytotoxicity induced by reactive oxygen species (ROS) was studied in detail. The results show that MNPs can be delivered into the lysosomes via classical incubation endocytic internalization; however, microbubbles and ultrasound allow the MNPs to pass through the cell membrane and enter the cytosol via a non-internalizing uptake route much more evenly and efficiently. Further, these different delivery routes result in different ROS levels and antioxidant capacities, as well as intracellular glutathione peroxidase activity for HepG2 cells. Our data indicate that the microbubble-ultrasound treatment method can serve as an efficient cytosolic delivery strategy to minimize long-term cytotoxicity of MNPs.

<p>In vitro Ultrasonic Potentiation of 2-Phenylethynesulfonamide/Magnetic Fluid Hyperthermia Combination Treatments for Ovarian Cancer</p>

“…23 The mechanisms associated with ultrasound-assisted internalization of nanoparticles have suggested that sonoporation leads to noninternalizing uptake routes, reducing oxidative stress and minimizing long-term cytotoxicity of nanoparticles in healthy cells. 24 Therefore, ultrasound provides a promising outlook in cancer treatment by improving drug/nanoparticle delivery, yet its incorporation as an integrated component in drug/MFH combination treatments has not been reported.…”

Sinapultide-Loaded Microbubbles Combined with Ultrasound to Attenuate Lipopolysaccharide-Induced Acute Lung Injury in Mice

“…The concentration of sinalpultide in suspension and microbubble was 0.1 mg/mL, and the ultrasound parameters were set as follows: frequency 0.5 MHz; intervention time 40 seconds; pressure 24.6 kPa. 15 After 24 hours incubation, cells were washed twice with PBS, MTT reagent was added to each well and co-incubated with cells for 4 hours at 37°C. The cell activity was determined by measuring the changes in absorbance at 490 nm using a microplate reader.…”

Magnetic drug delivery systems

“…However, subsequent studies have revealed that MNPs have pH-dependent peroxidase and catalase activities like those of certain enzymes. Chen et al [111,112] reported that iron oxide nanoparticles can catalyze H2O2 to produce the hydroxyl radical (·OH) under acidic conditions, and the hydroxyl radical is then able to oxidize a variety of organic molecules. That is, the MNPs have peroxidase-like activity.…”