Nanoparticles are a popular weapon for attacking cancer cells. Researchers typically load them with anticancer drugs to deliver payloads directly to malignant cells or heat the particles up to destroy tumor tissue. Two independent research teams have recently suggested a different tactic that involves trapping magnetic nanoparticles inside tiny cellular vesicles called lysosomes. A new study by one of those teams shows that when exposed to a moving magnetic field, these particles start spinning and tear up the lysosome walls, causing cell death.
Magnetic nanoparticles are used in an anticancer strategy known as hyperthermia. That’s because they generate heat, destroying tissue around them, when exposed to high-frequency alternating magnetic fields. Unfortunately, the strategy causes collateral damage to healthy tissue as well.
In 2013, Carlos Rinaldi, at the University of Florida, and his colleagues proposed a nonthermal technique for destroying tumors using magnetic nanoparticles (ACS Nano 2013, DOI: 10.1021/nn4007048). They targeted lysosomes, which act like trash collectors, engulfing foreign particles that enter cells. Applying alternating magnetic fields to iron oxide nanoparticles packed inside lysosomes caused the lysosomes to burst. But the researchers were unsure of the mechanism behind this destruction.
Another team has now demonstrated that the nanoparticles can be made to twirl and tear up lysosome walls (ACS Nano 2014, DOI: 10.1021/nn406302j). Erik Renström, of Lund University in Sweden, and his colleagues developed a device that generates a so-called dynamic magnetic field by moving or rotating a magnet over a sample. The torque generated by this field sets each nanoparticle rotating around its own axis.
To test the effects of the spinning particles in cells, the researchers used 100-nm-diameter iron oxide nanoparticles, which they coated with fluorescent dyes and antibodies that bind to proteins found on the outer membranes of lysosomes. They added the coated particles to cultures of rat pancreatic tumor cells and human pancreatic cells, and exposed them to a dynamic magnetic field for 20 minutes. By tracking the particles’ fluorescent signal, the researchers confirmed that metal oxide particles landed in the lysosomes.
Next, the researchers exposed the cultures to another 20-minute round of the magnetic field. If the nanoparticles were bound to the lysosome and started to spin, they should tear small holes in the membrane, the researchers thought. When the lysosomes ruptured, they would spill their contents into the cell, which would trigger cell death by releasing digestive enzymes and decreasing the cell’s pH. The researchers confirmed the lysosome rupture by staining the vesicles with a fluorescent dye that gets dimmer when lysosomes break open and their volume drops.
After applying the magnetic field once a day for six days, they found that cell growth dropped by almost 50% compared to untreated cells. The temperature of the culture did not spike over this time, so the researchers concluded that lysosome bursting and not heating led to cancer cell death.
Florida’s Rinaldi says the new study verifies his group’s proposal that magnetic nanoparticles can damage lysosomes. But he thinks that more proof is needed to show that nanoparticle rotation is the mechanism at work.
The new paper is an impressive proof of principle, says Challa Kumar, nanofabrication and nanomaterials director at Louisiana State University. Using spinning magnetic nanoparticles to destroy cancer cells is “a fantastic idea and it could open up a new line of investigation in cancer therapy.”