Localized delivery of an anti-cancer drug by remote-controlled microcarriers

Known for being the world’s first researcher to have guided a magnetic sphere through a living artery, Professor Martel,Director of the Nanorobotics Laboratory at Polytechnique Montréal, is announcing a spectacular new breakthrough in the field of nanomedicine. Using a magnetic resonance imaging (MRI) system, his team successfully guided microcarriers loaded with a dose of anti-cancer drug through the bloodstream of a living rabbit, right up to a targeted area in the liver, where the drug was successfully administered. This is a medical first that will help improve chemoembolization, a current treatment for liver cancer.

Biomaterials journal – Co-encapsulation of magnetic nanoparticles and doxorubicin into biodegradable microcarriers for deep tissue targeting by vascular MRI navigation

anorobotics Laboratory at Polytechnique Montréal Publications

Tabatabaei N., Lapointe J. and Martel S., “Shrinkable Hydrogel-based Magnetic Microrobots for Interventions in the Vascular Network”, International Journal of Advanced Robotics, Vol. 25 No. 8, Special Issue on Cordless Technology for Milli/Micro/Nano Robots, to be published in May 2011

Magnetic tumor targeting with external magnets is a promising method to increase the delivery of cytotoxic agents to tumor cells while reducing side effects. However, this approach suffers from intrinsic limitations, such as the inability to target areas within deep tissues, due mainly to a strong decrease of the magnetic field magnitude away from the magnets. Magnetic resonance navigation (MRN) involving the endovascular steering of therapeutic magnetic microcarriers (TMMC) represents a clinically viable alternative to reach deep tissues. MRN is achieved with an upgraded magnetic resonance imaging (MRI) scanner. In this proof-of-concept preclinical study, the preparation and steering of TMMC which were designed by taking into consideration the constraints of MRN and liver chemoembolization are reported. TMMC were biodegradable microparticles loaded with iron-cobalt nanoparticles and doxorubicin (DOX). These particles displayed high saturation magnetization (Ms = 72 emu g(-1)), MRI tracking compatibility (strong contrast on T2∗-weighted images), appropriate size for the blood vessel embolization (∼50 μm), and sustained release of DOX (over several days). The TMMC were successfully steered in vitro and in vivo in the rabbit model. In vivo targeting of the right or left liver lobes was achieved by MRN through the hepatic artery located 4 cm beneath the skin. Parameters such as flow velocity, TMMC release site in the artery, magnetic gradient and TMMC properties, affected the steering efficiency. These data illustrate the potential of MRN to improve drug targeting in deep tissues

The therapeutic magnetic microcarriers (TMMCs) were developed by Pierre Pouponneau, a PhD candidate under the joint direction of Professors Jean-Christophe Leroux and Martel. These tiny drug-delivery agents, made from biodegradable polymer and measuring 50 micrometers in diameter — just under the breadth of a hair — encapsulate a dose of a therapeutic agent (in this case, doxorubicin) as well as magnetic nanoparticles. Essentially tiny magnets, the nanoparticles are what allow the upgraded MRI system to guide the microcarriers through the blood vessels to the targeted organ. During the experiments, the TMMCs injected into the bloodstream were guided through the hepatic artery to the targeted part of the liver where the drug was progressively released. The results of these in-vivo experiments have recently been published in the prestigious journal Biomaterials and the patent describing this technology has just been issued in the United States

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