Magnetically controlled nanoparticles cause cancer cells to self-destruct

Avoid harming other tissues
April 4, 2014

SPIONs (Credit: ACS Nano)

Researchers at Lund University in Sweden have developed a technique to use magnetically controlled nanoparticles to force tumor cells to “self-destruct.” without harming surrounding tissue, as with radiotherapy, and tissues elsewhere in the body, as with chemotherapy.

“Our technique is able to attack only the tumor cells,” said Enming Zhang, first author of the study.

Inducing cell suicide

The technique involves getting the nanoparticles into a tumor cell, where they bind to lysosomes, which can break down foreign substances that have entered a cell. They can also break down the entire cell through a process known as apoptosis (controlled cell death), a type of destruction where damaged cells dissolve themselves.

The researchers used superparamagnetic nanoparticles of iron oxide. Once the particles are inside the cancer cells, the cells are exposed to an external magnetic field, and the nanoparticles begin to rotate in a way that causes the lysosomes to start destroying the cells.

Previous attempts to use superparamagnetic nanoparticles.have focused on using the external field to create heat that kills the cancer cells. The problem with this is that the heat can cause inflammation that risks harming surrounding, healthy tissue. The new method, on the other hand, in which the rotation of the magnetic nanoparticles can be controlled, only affects the tumor cells that the nanoparticles have entered.

The new technique is primarily intended for cancer treatment, but according to the researchers, it can be used for other diseases, including autoimmune diseases such as type 1 diabetes, in which the immune system attacks the body’s own insulin production.

The researchers at Lund University have a patent pending for their technique with the rotating nanoparticles. However, a lot of work remains before it can be transferred from the laboratory to clinical trials on patients.

The study, a collaboration between physicists, chemists, engineers and doctors from Sweden, Germany and the U.S., was published in the journal ACS Nano.

Abstract of ACS Nano paper

The ability to control the movement of nanoparticles remotely and with high precision would have far-reaching implications in many areas of nanotechnology. We have designed a unique dynamic magnetic field (DMF) generator that can induce rotational movements of superparamagnetic iron oxide nanoparticles (SPIONs). We examined whether the rotational nanoparticle movement could be used for remote induction of cell death by injuring lysosomal membrane structures. We further hypothesized that the shear forces created by the generation of oscillatory torques (incomplete rotation) of SPIONs bound to lysosomal membranes would cause membrane permeabilization, lead to extravasation of lysosomal contents into the cytoplasm, and induce apoptosis. To this end, we covalently conjugated SPIONs with antibodies targeting the lysosomal protein marker LAMP1 (LAMP1-SPION). Remote activation of slow rotation of LAMP1-SPIONs significantly improved the efficacy of cellular internalization of the nanoparticles. LAMP1-SPIONs then preferentially accumulated along the membrane in lysosomes in both rat insulinoma tumor cells and human pancreatic beta cells due to binding of LAMP1-SPIONs to endogenous LAMP1. Further activation of torques by the LAMP1-SPIONs bound to lysosomes resulted in rapid decrease in size and number of lysosomes, attributable to tearing of the lysosomal membrane by the shear force of the rotationally activated LAMP1-SPIONs. This remote activation resulted in an increased expression of early and late apoptotic markers and impaired cell growth. Our findings suggest that DMF treatment of lysosome-targeted nanoparticles offers a noninvasive tool to induce apoptosis remotely and could serve as an important platform technology for a wide range of biomedical applications.