Magneto-mechanical treatment of human glioblastoma cells with engineered iron oxide powder microparticles for triggering apoptosis

Abstract

In nanomedicine, treatments based on physical mechanisms are more and more investigated and are promising alternatives for challenging tumor therapy. One of these approaches, called magneto-mechanical treatment, consists in triggering cell death via the vibration of anisotropic magnetic particles, under a low frequency magnetic field. In this work, we introduce a new type of easily accessible magnetic microparticles (MMPs) and study the influence of their surface functionalization on their ability to induce such an effect, and its mechanism. We prepared anisotropic magnetite microparticles by liquid-phase ball milling of a magnetite powder. These particles are completely different from the often-used SPIONs: they are micron-size, ferromagnetic, with a closed-flux magnetic structure reminiscent of that of vortex particles. The magnetic particles were covered with a silica shell, and grafted with PEGylated ligands with various physicochemical properties. We investigated both bare and coated particles' in vitro cytotoxicity, and compared their efficiency to induce U87-MG human glioblastoma cell apoptosis under a low frequency rotating magnetic field (RMF). Our results indicated that (1) the magneto-mechanical treatment with bare MMPs induces a rapid decrease in cell viability whereas the effect is slower with PEGylated particles; (2) the number of apoptotic cells after magneto-mechanical treatment is higher with PEGylated particles; (3) a lower frequency of RMF (down to 2 Hz) favors the apoptosis. These results highlight a difference in the cell death mechanism according to the properties of particles used-the rapid cell death observed with the bare MMPs indicates a death pathway via necrosis, while PEGylated particles seem to favor apoptosis.