Toward Accumulation of Magnetic Nanoparticles into Tissues of Small Porosity

Abstract

Magnetic concentration of drug-laden magnetic nanoparticles has been proven to increase the delivery efficiency of treatment by 2-fold. In these techniques, particles are concentrated by the presence of a magnetic source that delivers a very high magnetic field and a strong magnetic field gradient. We have found that such magnetic conditions cause even 150 nm particles to aggregate significantly into assemblies that exceed several micrometers in length within minutes. Such assembly sizes exceed the effective intercellular pore size of tumor tissues preventing these drug-laden magnetic nanoparticles from reaching their target sites. We demonstrate that by using dynamic magnetic fields instead, we can break up these magnetic nanoparticles while simultaneously concentrating them at target sites. The dynamic fields we investigate involve precessing the field direction while maintaining a field gradient. Manipulating the field direction drives the particles into attractive and repulsive configurations that can be tuned to assemble or disassemble these particle clusters. Here, we develop a simple analytic model to describe the kinetic thresholds of disassembly and we compare both experimental and numerical results of magnetic particle suspensions subjected to dynamic fields. Finally we apply these methods to demonstrate penetration in a porous scaffold with a similar pore size to that expected of a tumor tissue.

Rotating colloids in rotating magnetic fields: Dipolar relaxation and hydrodynamic coupling

“…Previous research suggests that hydrodynamic interactions and dipole relaxation both affect the frequency dependence of magnetic doublet rotation in rotating fields. It has been observed that doublets rotate at the same frequency as rotating fields up to a critical frequency, after which the rotation rate declines due to viscous drag [8,23,28,29]. These studies showed at frequencies slightly higher than the critical frequency: (1) individual dipoles no longer remain aligned along the line of centers, (2) for freely rotating doublets, the interparticle distance oscillates, and (3) for both rigid and freely rotating doublets, the angular trajectories oscillate about an average steady rotational velocity.…”

Functional Nanoparticles for Tumor Penetration of Therapeutics

“…Under a dynamic magnetic field, the switchable magnetic field direction can cause the particles to group into an attractive or repulsive configuration, promoting the particle clusters to assemble or disassemble. Thus, this reverse property was utilized to create a simple analytical model to evaluate the kinetic thresholds of the assembly and disassembly of magnetic nanoparticles, and these methods demonstrated good tumor penetration into a gel with a similar pore size as that of tumor tissue [18].…”

Studies on Aggregated Nanoparticles Steering during Deep Brain Membrane Crossing

“…Therefore, previously in a simulation, we solved the sticking issue by intentionally changing the magnetic field direction, and the use of dynamic magnetic actuation (change in field direction) for reducing aggregation [ 21 ]. The experimental results in [ 22 ] showed that the dynamic actuation with a pulse-shaped magnetic field using permanent magnets can improve crossing of the cell barrier.…”