The paper describes the concept of magneto-mechanical actuation of single-domain magnetic nanoparticles (MNPs) in super-low and low frequency alternating magnetic fields (AMFs) and its possible use for remote control of nanomedicines and drug delivery systems. The applications of this approach for remote actuation of drug release as well as effects on biomacromolecules, biomembranes, subcellular structures and cells are discussed in comparison to conventional strategies employing magnetic hyperthermia in a radio frequency (RF) AMF. Several quantitative models describing interaction of functionalized MNPs with single macromolecules, lipid membranes, and proteins (e.g. cell membrane receptors, ion channels) are presented. The optimal characteristics of the MNPs and an AMF for effective magneto-mechanical actuation of single molecule responses in biological and bio-inspired systems are discussed. Altogether, the described studies and phenomena offer opportunities for the development of novel therapeutics both alone and in combination with magnetic hyperthermia.

Magnetomechanical modulation of biochemical processes is a promising instrument for bioengineering and nanomedicine. This work demonstrates two approaches to control activity of an enzyme, α-chymotrypsin immobilized on the surface of gold-coated magnetite magnetic nanoparticles (GM-MNPs) using a nonheating low-frequency magnetic field (LF MF). The measurement of the enzyme reaction rate was carried out in situ during exposure to the magnetic field. The first approach involves α-chymotrypsin-GM-MNPs conjugates, in which the enzyme undergoes mechanical deformations with the reorientation of the MNPs under LF MF (16-410 Hz frequency, 88 mT flux density). Such mechanical deformations result in conformational changes in α-chymotrypsin structure, as confirmed by infrared spectroscopy and molecular modeling, and lead to a 63% decrease of enzyme initial activity. The second approach involves an α-chymotrypsin-GM-MNPs/trypsin inhibitor-GM-MNPs complex, in which the activity of the enzyme is partially inhibited. In this case the reorientation of MNPs in the field leads to disruption of the enzyme-inhibitor complex and an almost 2-fold increase of enzyme activity. The results further demonstrate the utility of magnetomechanical actuation at the nanoscale for the remote modulation of biochemical reactions.

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Remote nano-magneto-mechanical actuation of magnetic nanoparticles (Mnps) by non-heating extremely low frequency magnetic field (ELF MF) is explored as a tool for non-invasive modificationof bionanomaterials in pharmaceutical and medical applications. Here we study the effects of ELF MF (30-160 Hz, 8-120 kA/m) on the activity and release of a model enzyme, superoxide dismutase 1 (SOD1) immobilized by polyion coupling on dispersed Mnps aggregates coated with poly(L-lysine)-blockpoly(ethylene glycol) block copolymer (s-MNPs). Such fields do not cause any considerable heating of Mnps but promote their rotating-oscillating mechanical motion that produces mechanical forces and deformations in adjacent materials. We observed the changes in the catalytic activity of immobilized SOD1 as well as its release from the s-MNPs/SOD1 polyion complex upon application of the ELF MF for 5 to 15 min. At longer exposures (25 min) the s-MNPs/SOD1 dispersion destabilizes. The bell-shaped effect of the field frequency with maximum at f = 50 Hz and saturation effect of field strength (between 30 kA/m and 120 kA/m at f = 50 Hz) are reported and explained. The findings are significant as one early indication of the nano-magneto-mechanical disruption by eLf Mf of cooperative polyion complexes that are widely used for design of current functional healthcare bionanomaterials.Non-invasive functional control of bionanomaterials in inaccessible areas of a human body (e.g., biochemical reactions, drug release, gene expression, etc.) could greatly advance development of diagnostics and therapeutic modalities 1 . This control can be accomplished by remote actuation of nanoparticles by external fields 2-6 . In recent years magnetic nanoparticles (MNPs) have been investigated for cell separation, targeted drug delivery, and magnetic resonance imaging (MRI) 7-9 . Remote actuation of MNPs by radio frequency (200-800 kHz) magnetic fields has been used in hyperthermia for cancer therapy 10-12 . However, this approach has a risk of tissue overheating and damage. Recently an alternative nano-magneto-mechanical actuation of MNPs by non-heating extremely low frequency magnetic field (ELF MF) has attracted increasing attention in drug delivery and nanomedicine [13][14][15][16][17] .The phenomenon of nano-magneto-mechanical actuation is linked to the ability of MNPs to undergo mechanical motion in ELF MF and as a consequence produce mechanical forces and deformations in adjacent materials. It is well known, that a single-domain MNPs can relax in an external magnetic field, reducing an angle between the MNPs magnetic moment μ and the field vector H [18][19][20] . Two basic types of relaxation phenomena are dependent on the size of the magnetic core. MNPs with D m less than some critical value d* experience rotation of magnetic moments μ towards the vector H, which proceeds mainly by overcoming the crystallographic anisotropy of the lattice, without causing significant mechanical motion of the particle (Néel relaxation). MNPs with a diameter D m greater than d*...