Question

Hierarchically structured magnetic nanoconstructs with enhanced relaxivity and cooperative tumor accumulation

Answer 1

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.