Remote Actuation of Magnetic Nanoparticles For Cancer Cell Selective Treatment Through Cytoskeletal Disruption

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

Magnetic Block Ionomer Complexes for Potential Dual Imaging and Therapeutic Agents

Magnetic block ionomer complexes (MBICs) containing a combination of therapeutic and imaging agents are of great interest for delivering drugs and tracking their biodistribution with magnetic resonance imaging. With an aim to develop nanocarriers with high drug loadings that integrate magnetic nanoparticles into one system, we herein report antibiotic-laden MBICs based on assembly of poly­(ethylene oxide-<i>b</i>-acrylate) (PEO-<i>b</i>-PAA) ionomers with nanomagnetite and gentamicin. The polymer was bound to the magnetic nanoparticle surfaces via ligand adsorption of the PAA block, thereby creating a double corona structure with a nonionic PEO shell and an ionic region rich in PAA. The portion of carboxylates that were not bound to the magnetite provided binding sites for drug loading via ionic complexation. PEO was chosen as a block copolymer segment to improve biocompatibility and aid in dispersion through interparticle steric repulsion. Intensity average diameters increased from 34 to 62 nm upon adding the drug, suggesting that the particles formed small clusters. Zeta potentials decreased from approximately −40 without gentamicin to approximately −10 mV with the drug, indicating that the drug effectively localized the charges in the MBIC cores. Approximately 35 wt % of the encapsulated gentamicin was released under physiological conditions within 10 h, and this was followed by slower release of another 7% by 18 h. The solid magnetite core serves as a multifunctional substrate for block ionomers to stably adsorb, thus acting as a pseudo-crosslinking site in the complexes that enhances their stability. Complexes between PEO-<i>b</i>-PAA and gentamicin without magnetite instantaneously dissociate in saline buffer. When the same copolymer was adsorbed onto magnetite, subsequent complexation with gentamicin resulted in stable complexes that withstood media with physiological ionic strength