Magnetic Resonance Navigation (MRN) relies on Magnetic Nanoparticles (MNPs) embedded in microcarriers or microrobots to allow the induction of a directional propelling force by 3-D magnetic gradients. These magnetic gradients are superposed on a sufficiently high homogeneous magnetic field (e.g. the Bo field of a MR scanner) to achieve maximum propelling force through magnetization saturation of the MNPs. As previously demonstrated by our group, such technique was successful at maintaining microcarriers along a planned trajectory in the blood vessels based on tracking information gathered using Magnetic Resonance Imaging (MRI) sequences from artifacts caused by the same MNPs. Besides propulsion and tracking, the same MNPs can be synthesized with characteristics that can allow for the diffusion of therapeutic cargo carried by these MR-navigable carriers through the Blood Brain Barrier (BBB) using localized hyperthermia without compromising the MRN capabilities. In the present study, localized hyperthermia induced by an alternating magnetic field (AC field) is investigated for the purpose of transient controlled disruption of the BBB and hence local delivery of therapeutic agents into the brain. Here, an external heating apparatus was used to impose a regional heat shock on the skull of a living mouse model. The effect of heat on the permeability of the BBB was assessed using histological observation and tissue staining by Evans blue dye. Results show direct correlation between hyperthermia and BBB leakage as well as its recovery from thermal damage. Therefore, in addition to on-command propulsion and remote tracking, the proposed navigable agents could be suitable for controlled opening of the BBB by hyperthermia and selective brain drug delivery.

Our group has previously demonstrated that magnetic nanoparticles (MNP) embedded in microrobots can be used for propulsion and tracking in the human vascular network while being guided by an MRI platform. Here, we show that the same magnetic nanoparticles can also be exploited to perform various functions including but not limited to hyperthermic drug release actuators. Specifically, we synthesized vascular microrobots by embedding MNP in N-isopropylacrylamide (NIPA) thermo responsive hydrogel. We experimentally demonstrate the decrease in volume of the hydrogel microrobot in response to AC magnetic heating, a property that allows microrobots to adapt to blood vessels of various diameters. This type of hydrogel is not only able to reduce size in response to temperature elevations but it can also be used to release possible therapeutic agents previously trapped within the hydrogel. Here, NIPA hydrogel samples were placed inside an AC magnetic field of 116 Oe at 145 kHz. Temperature elevations as well as change in hydrogel volume were recorded.