Microrobotic navigable entities for Magnetic Resonance Targeting

Abstract

Magnetic Resonance Targeting (MRT) uses MRI for gathering tracking data to determine the position of microscale entities with the goal of guiding them towards a specific target in the body accessible through the vascular network. At full capabilities, a MRT platform designed to treat a human would consist of a clinical MRI scanner running special algorithms and upgraded to provide propulsion gradient up to approximately 400mT/m to enable entities as small as a few tens of micrometers in diameter and containing magnetic nanoparticles (MNP) to be steered at vessel bifurcations based on tracking information. Indeed, using a clinical MRI system, we showed that such single entity with a diameter as small as 15microm is detectable in gradient-echo scans. Among many potential interventions, targeted cancer therapy is a good initial application for such new microrobotic approach since secondary toxicity for the patient could be reduced while increasing therapeutic efficacy using lower dosages. Although many types of such entities are needed to provide a larger set of tools, here, only three initial types designed with different functionalities and for different types of cancer are briefly described. Initially designed for targeted chemo-embolization of liver tumors, the first type known as Therapeutic Magnetic Micro-Carriers (TMMC) consists in its present form of approximately 50 microm PLGA microparticles containing therapeutics and approximately 180 nm FeCo MNP. For the second type, MNP are not only used for propulsion and tracking, but also actuation based on a local elevation of the temperature. In its simplest form, it consists of approxiamtely 20 nm MNP embedded in a thermo-sensitive hydrogel known as PNIPA, allowing additional functionalities such as computer triggered drug release and targeted hyperthermia. The third type initially considered to target colorectal tumors, consists of 1-2 microm MR-trackable and controllable MC-1 Magnetotactic Bacteria (MTB) with propelling thrust force provided by two flagella bundles per cell exceeding 4 pN.