Targeted delivery of therapeutic agents with controlled bacterial carriers in the human blood vessels

Summary form only given. The treatment of cancer is one of the most challenging tasks of modern medicine and secondary toxicity remains a critical issue. Although intra-arterial chemotherapy or chemo-embolization provides interesting success, the release of drug in the systemic circulation prevents high intra-tumoral drug concentration to be sustained. Hence, targeting specifically the tumor cells becomes a major goal of modern oncology. As such, providing means of carrying microparticles for specific endovascular drug delivery or radioisotopes at the site of the tumor mass would be extremely attractive. Although we have shown experimentally that a clinical magnetic resonance imaging (MRI) system can propel a ferromagnetic core in a human cardiovascular network through an induced force generated by the same magnetic gradients used for MR-imaging, it becomes technological very challenging to apply this method to navigate particles in a 3D space in order to reach the tumor cells through an anarchic arteriolocapillar network stimulated by tumoral angiogenesis. Since the induction of a propulsion force decreases significantly for much smaller particles, propulsion in capillaries would require gradient amplitudes that are technologically and practically not an alternative considering the size and cooling issues of an additional gradient coils systems embedded in the MRI bore. Our proposed concept consists of using magnetotactic bacteria to push microbeads being coated with therapeutic agents in the capillary network. We have shown that the displacement path of a magnetotactic bacterium pushing a microbead can be modified by changing the orientation of the lines of a magnetic field. Preliminary experimental results also showed that magnetotactic bacteria of type MC-1 could swim efficiently in human blood and that a swarm of these bacteria could potentially be detected by MR-imaging. Although the DC magnetic field of clinical MRI systems complicates the directional control of such bacteria compared with an X-ray system that could be upgraded with peripheral permanent or electro-magnets, the use of an MRI system has many advantages in term of imaging modalities and the lack of radiation. We report preliminary studies related to local perturbations of the DC magnetic field of a clinical MRI system time multiplexed with imaging sequences that could allow the target delivery of therapeutic agents through microbeads being pushed by magnetotactic bacteria operating under computer control