MRI-Compatible Injection System for Magnetic Microparticle Embolization.

OBJECTIVE: Dipole field navigation and magnetic resonance navigation exploit B0 magnetic fields and imaging gradients for targeted intra-arterial therapies by using magnetic drug-eluting beads (MDEBs). The strong magnetic strength (1.5 or 3 T) of clinical magnetic resonance imaging (MRI) scanners is the main challenge preventing the formation and controlled injection of specific-sized particle aggregates. Here, an MRI-compatible injector is proposed to solve the above problem. METHODS: The injector consists of two peristaltic pumps, an optical counter, and a magnetic trap. The magnetic property of microparticles, the magnetic compatibility of different parts within the injector, and the field distribution of the MRI system were studied to determine the optimal design and setup of the injector. The performance was investigated through 30.4-emu/g biocompatible magnetic microparticles (230 ± 35 µm in diameter) corresponding to the specifications needed for trans-arterial chemoembolization in human adults. RESULTS: The system can form aggregates containing 20 to 60 microparticles with a precision of six particles. The corresponding aggregate lengths range from 1.6 to 3.2 mm. Based on the injections of 50 MRI-visible boluses into a phantom which mimics realistic physiological conditions, 82% of the aggregates successfully reached subbranches. CONCLUSION AND SIGNIFICANCE: This system has the capability to operate within the strong magnetic field of a clinical 3-T MRI, to form proper particle aggregates and to automatically inject these aggregates into the MRI bore. Moreover, the versatility of the proposed injector renders it suitable for selective injections of MDEBs during MR-guided embolization procedures.

Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions.

Oxygen-depleted hypoxic regions in the tumour are generally resistant to therapies. Although nanocarriers have been used to deliver drugs, the targeting ratios have been very low. Here, we show that the magneto-aerotactic migration behaviour of magnetotactic bacteria, Magnetococcus marinus strain MC-1 (ref. 4), can be used to transport drug-loaded nanoliposomes into hypoxic regions of the tumour. In their natural environment, MC-1 cells, each containing a chain of magnetic iron-oxide nanocrystals, tend to swim along local magnetic field lines and towards low oxygen concentrations based on a two-state aerotactic sensing system. We show that when MC-1 cells bearing covalently bound drug-containing nanoliposomes were injected near the tumour in severe combined immunodeficient beige mice and magnetically guided, up to 55% of MC-1 cells penetrated into hypoxic regions of HCT116 colorectal xenografts. Approximately 70 drug-loaded nanoliposomes were attached to each MC-1 cell. Our results suggest that harnessing swarms of microorganisms exhibiting magneto-aerotactic behaviour can significantly improve the therapeutic index of various nanocarriers in tumour hypoxic regions.