One potentially valuable way to attack cancer cells is to zap them with low-intensity alternating current. This interferes with the flow of calcium and potassium ions in and out of the cells, a process so important that disrupting it ultimately kills them.
But there is a problem with this approach: healthy cells are just as susceptible to ion channel disruption as cancer cells, so the treatment kills healthy and cancerous cells alike. What’s needed is a way to focus the treatment on cancer cells while leaving the healthy ones untouched.
Enter Attilio Marino at the Istituto Italiano di Tecnologia, Enrico Almici at the Polytechnic University of Turin, and colleagues in Italy. These guys use piezoelectric nanoparticles that generate current inside the body when repeatedly compressed with ultrasound. And they have gathered the first evidence that this could be turned into an effective treatment for cancer.
The technique is straightforward in theory. Piezoelectric materials generate a charge when squeezed (and similarly change shape when zapped with a voltage). They are widely used in everything from microphones to motors.
Marino and co’s idea is to inject biocompatible nanoparticles into the body and then bombard them with ultrasound. The high and low pressures associated with the ultrasound should cause the nanoparticles to generate a charge that interferes with ion channels and kills the cells. The team choose barium titanate nanoparticles, which are considered biocompatible since they contain no lead.
The team have also developed an important targeting mechanism. The nanoparticles must be designed to attach themselves to cancerous cells while ignoring healthy ones. Marino and co achieve this by coating the nanoparticles with a plastic polymer and then coating this shell with antibodies that bind to a receptor associated with a specific type of cancer cell.
In this case, the team focus on an aggressive type of brain cancer called glioblastoma multiforme. The membranes of these cells express transferrin receptors, unlike most healthy cells. So the team coat their nanoparticles with transferrin antibodies, which bind to transferrin receptors. That turns the nanoparticles into guided missiles that target only cancer cells.
The nanoparticles must also pass through the blood-brain barrier, an important factor in brain cancer treatment. Nanoparticles can do this if they are small enough. So the team chose particles 300 nanometers in diameter, which is within the size range that can pass through the barrier.
Marino and co tested their approach in vitro, growing brain tumors in the lab in such a way that they are covered by an endothelial barrier that acts like the blood-brain barrier. The researchers then measured how well the nanoparticles penetrated this barrier.
Next, they bombarded the samples with ultrasound and administered a standard chemotherapy drug called temozolomide.
The results: the team say the nanoparticles are able to penetrate the cancer cells with relative ease. And when inside the cancer cells and bombarded with ultrasound, the nanoparticles significantly increase the efficacy of temozolomide.
Using both chemical and electrophysical approaches shows good potential for improving brain cancer treatment. “The chronic piezoelectric stimulation, in synergic combination with a sub-toxic concentration of temozolomide, induced an increased sensitivity to chemotherapy treatment and remarkable anticancer effects,” say Marino and co.
However, there are issues to overcome before this can be thought of as a potential treatment. The model that Marino and co use is far simpler than the conditions inside real bodies. The team plan to test more complex models and to look at the treatment’s efficacy in vivo. They also plan to look at nanoparticles with sizes and shapes that allow better control over piezoelectric effects.
That has potential, in particular, for targeting microscopic residual tumors that are the main cause of disease recurrence after surgery. There may be a long way to go, but this kind of nanomedicine is beginning to show its promise.
Ref: arxiv.org/abs/1812.08248 : Piezoelectric Barium Titanate Nanostimulators for the Treatment of Glioblastoma Multiforme
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