Un article de Laboratoire de nanorobotique.

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Note: Only the projects where the Director of the NanoRobotics Laboratory is the Principal Investigator are listed here

Development of an upgraded MRI-based platform for tumor targeting and drug delivery

This project is based on our previous development of fundamental techniques and methods for the propulsion and navigation of ferromagnetic cores in the cardiovascular system through the induction of force from magnetic gradients generated by a clinical Magnetic Resonance Imaging (MRI) system.

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 rapid distribution of the drug in the whole body prevents high intra-tumoral drug concentrations to be sustained. Hence, targeting specifically the tumor cells becomes a major goal of modern oncology. As such, providing means of carrying nanoparticles for specific endovascular drug or radioisotopes delivery at the site of the tumor mass would be extremely attractive. The aim of this project is to develop a new method to enhance the treatment efficacy for future potential uses in human through the development of new magnetic carriers with improved targeting using three-dimensional induced controlled forces from magnetic gradients generated by an upgraded clinical Magnetic Resonance Imaging (MRI) system. Unlike presently known magnetic targeting techniques, the imaging feedbacks and computerized control of 3D magnetic gradients generations provided by a clinical MRI system coupled with a carrier based on an agglomeration of nanoparticles made of materials with high saturation magnetization, potentially allow for precise delivery and targeting of a tumor located deeply in the body.

More specifically, this project aims at investigating the possibility of improving the targeting of tumor cells for future targeted chemotherapy, chemo-embolization and/or local hyperthermia through the induction of propulsion forces generated by magnetic gradients from an upgraded clinical MRI system on magnetic carriers for future use in human. The experimental focus is on the direct delivery and sustainability of magnetic particles acting as potential carriers for researchers to test and to deliver a variety of therapeutic agents directly into the tumor mass through the use of a clinical MRI system upgraded through additional dedicated software and hardware modules. The specific aims are: 1. Assess the delivery of ferromagnetic cores in the arterioles; 2. Assess the arteriolocapillar network entry of ferromagnetic particles; and 3. Assess navigation of ferromagnetic particles in vivo through tumor-induced capillary networks with sustainability in the tumor mass. This proposed platform will be a valuable tool to help enhance the efficiency of cancer threatments while improving patients recovery time.

MRI-based tumor targeting enhancement with magnetotactic bacterial carriers

The delivery of a therapeutic agent through controlled carriers directly to the tumoral lesion can enhance treatment efficacy by reducing dosage while minimizing systemic circulation of toxic compounds through healthy tissues. As such, the induction of a feedback controlled steering force on ferromagnetic carriers from magnetic gradients generated by an upgraded clinical MRI system has been demonstrated by our group. But the gradient strengths required in some sections of the capillary network surrounding a tumor may be technologically very difficult to achieve for human due mainly to the size and cooling issues of additional gradient coils embedded in the MRI bore. As such, the use of MC-1 Magnetotactic Bacteria (MTB) pushing microbeads with therapeutic agent and nanoparticles to allow real-time tracking with the MRI system of the bacteria may provide complementary means of propulsion in smaller capillaries. More specifically, the aim of this project is to exploit the property of the chain of magnetic single domain nanoparticles (50-100 nm in size) called magnetosomes embedded in each MTB and acting as a navigational compass inside each bacterium combined with the very effective trust provided by the molecular motor of the bacteria to enhance targeting. Navigation control of such bacterial carriers will be performed by changing the direction of the magnetic field under computer control to “migrate” such bacteria towards the tumoral region.

Development of biocarriers and biosensors designed specifically to be navigated deeply in the human body with the use of an upgraded clinical MRI platform

New biocarriers and biosensors made of ferromagnetic particles and special polymeric materials reacting to environmental changes such as pH or oxygen level are being investigated. The integration of ferromagnetic particles allows potential MR-tracking and automatic delivery of these biosensors through induced forces generated by magnetic gradients from an upgraded MRI system to locations inaccessible with any existing technologies. Automatic delivery of these biosensors to specific regions of the brain through the blood-brain barrier is of special interest. This technology may provide an instrument to image and to study brain functions at a higher spatial resolution and non-invasively, with potential use in future brain-machine interfaces. Agglomerations of several of these biosensors can take place when the pH or the oxygen level related to brain activities occurs, shifting the resonant frequency to a lower value when modulated. The corresponding information could theoretically be used to image such functions. Proving the feasibility of this approach is the main objective of this project.