Abstract
Motion of micron and sub-micron size magnetic particles in alternating magnetic fields can activate mechanosensitive cellular functions or physically destruct cancer cells. However, such effects are usually observed with relatively large magnetic particles (>250 nm) that would be difficult if at all possible to deliver to remote sites in the body to treat disease. Here we show a completely new mechanism of selective toxicity of superparamagnetic nanoparticles (SMNP) of 7 to 8 nm in diameter to cancer cells. These particles are coated by block copolymers, which facilitates their entry into the cells and clustering in the lysosomes, where they are then magneto-mechanically actuated by remotely applied alternating current (AC) magnetic fields of very low frequency (50 Hz). Such fields and treatments are safe for surrounding tissues but produce cytoskeletal disruption and subsequent death of cancer cells while leaving healthy cells intact.
Highlights
Several studies document cell damage with exposure to alternating current (AC) magnetic fields even without a perceptible increase in temperature[9,10,11,12,13,14]
Distinct from these studies, here we show a novel magneto-mechanical mechanism of action of small polymer coated superparamagnetic nanoparticles (SMNP) actuated inside the cells, by super low frequency AC magnetic fields as discussed in previous reports of magneto-mechanical actuation[14,15]
The polyanion block was either polyacrylic acid (PAA) or polymethacrylic acid (PMA), which differ in their hydrophobicity
Summary
Several studies document cell damage with exposure to AC magnetic fields even without a perceptible increase in temperature[9,10,11,12,13,14]. Zhang et al designed a rotating AC magnetic field space with a field strength of ~30 mT and exposed cells at a very low frequency of ~20 Hz14 They utilized the field to enhance uptake of iron oxide nanoparticles of 100 nm and above that were conjugated with antibodies for targeting the lysosomal protein marker LAMP-1 Into rat insulinoma tumor cells and human pancreatic cells. The glioblastoma cells underwent apoptosis and it was hypothesized that the discs aligned in the field and somewhat misaligned when the field was changed, damaging the cell membranes that they were bound to, and further causing in an ionic signal that resulted in cell apoptosis[15] Distinct from these studies, here we show a novel magneto-mechanical mechanism of action of small polymer coated SMNPs actuated inside the cells, by super low frequency AC magnetic fields as discussed in previous reports of magneto-mechanical actuation[14,15]. We show that a non-targeted polymer coated SMNP system is taken up into cell lysosomal compartments and after magnetic field actuation, can cause cytoskeletal disruption in cancer cells while leaving healthy cells intact and viable
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