Submicroscopic particles that contain even smaller particles of iron oxide could make magnetic resonance imaging (MRI) a far more powerful tool to detect and fight disease.
Scientists at Rice University and Methodist Hospital Research Institute (MHRI) led an international team of researchers in creating composite particles that can be injected into patients and guided by magnetic fields. Once in position, the particles may be heated to kill malignant tissues or trigger the release of drugs at the site.
The “nanoconstructs” should fully degrade and leave the body within a few days, they reported.
They packaged thousands of iron oxide particles – with magnetic cores as small as 5 nanometers across – inside larger particles.
The researchers made two such nanoconstructs, embedding iron oxide particles in silicon mesoporous particles (SiMPs) and discoidal polymeric nanoconstructs (DPNs). They knew from previous research that submicron-sized SiMPs and DPNs naturally accumulate within the tumor’s blood vessels.
Iron oxide enhances the ability to position and hold the particles in place with magnets, said lead author and Rice graduate student Ayrat Gizzatov. “They get attracted by the magnet, and that induces another dipole-dipole magnetic interaction among the particles and increases their interparticle communication mechanism,” he said.
Tests showed iron oxide particles made the nanoconstructs 10 times better than traditional contrast agents with what amounted to significantly lower doses of iron than used in current practice.
The new research also showed that, as a general principle, confining MRI contrast agents (like iron oxide) in geometric structures enhances their relaxivity – the property that makes the agents appear in MRI images. (The shorter the relaxation time, the greater the contrast in the image.)
While the particles are too big to target specific proteins, Gizzatov said it might also be possible to modify them with elements that will increase their accumulation in tumors.
Iron oxide nanoparticles are formidable multifunctional systems capable of contrast enhancement in magnetic resonance imaging, guidance under remote fields, heat generation, and biodegradation. Yet, this potential is underutilized in that each function manifests at different nanoparticle sizes. Here, sub-micrometer discoidal magnetic nanoconstructs are realized by confining 5 nm ultra-small super-paramagnetic iron oxide nanoparticles (USPIOs) within two different mesoporous structures, made out of silicon and polymers. These nanoconstructs exhibit transversal relaxivities up to ≈10 times (r 2 ≈ 835 mm −1 s−1) higher than conventional USPIOs and, under external magnetic fields, collectively cooperate to amplify tumor accumulation. The boost in r 2 relaxivity arises from the formation of mesoscopic USPIO clusters within the porous matrix, inducing a local reduction in water molecule mobility as demonstrated via molecular dynamics simulations. The cooperative accumulation under static magnetic field derives from the large amount of iron that can be loaded per nanoconstuct (up to ≈65 fg) and the consequential generation of significant inter-particle magnetic dipole interactions. In tumor bearing mice, the silicon-based nanoconstructs provide MRI contrast enhancement at much smaller doses of iron (≈0.5 mg of Fe kg−1 animal) as compared to current practice.
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