Therapeutic Magnetic Microcarriers Guided by Magnetic Resonance Navigation for Enhanced Liver Chemoembilization: A Design Review
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This review paper describes the past, present and future design of therapeutic magnetic carriers (TMMC) being guided in the vascular network using a novel technique known as magnetic resonance navigation (MRN). This targeting method is an extension of magnetic resonance imaging (MRI) technologies. MRN, based on magnetic gradient variation, aims to navigate carriers in real-time along a pre-planned trajectory from their injection site to a targeted area. As such, this approach should minimize systemic distribution of toxic agents loaded into the carriers and improve therapeutic efficacy by delivering a larger proportion of the drug injected. MRN-compatible carriers (shape, material, size, magnetic properties, biocompatibility) have to be designed by taking into consideration the constraints of the medical task and MRN. In the past, as a proof of concept of MRN feasibility, a 1.5-mm ferromagnetic bead was guided in the artery of a living swine with a clinical MRI system. Present day, to aim at medical applications, TMMC have been designed for targeted liver chemoembolization by MRN. TMMC are 50-μm biodegradable microparticles loaded with iron-cobalt nanoparticles and doxorubicin as an antitumor drug. TMMC were selectively guided to the right or left liver lobes in a rabbit model with a clinical MRI scanner upgraded with steering coils. To treat human liver tumor, according to the theoretical MRN model, future TMMC design should take into consideration magnetic nanoparticle properties (nature and loading), MRN platform performances (gradient amplitude and rise time) and vascular hepatic network properties (blood flow velocity and geometry) to optimize the carrier diameter for efficient chemoembolization.
KeywordsMagnetic tumor targeting Magnetic resonance imaging (MRI) Magnetic nanoparticles Microparticles Drug delivery
This work was supported by the Canadian Institutes for Health Research (CIHR), the Canada Research Chair program, the Canada Foundation for Innovation (CFI), the Natural Sciences and Engineering Research Council of Canada (NSERC), and Fonds Québécois de la Recherche sur la Nature et les Technologies (FQRNT).
- 9.Chorny, M., I. Fishbein, B. B. Yellen, I. S. Alferiev, M. Bakay, S. Ganta, R. Adamo, M. Amiji, G. Friedman, and R. J. Levy. Targeting stents with local delivery of paclitaxel-loaded magnetic nanoparticles using uniform fields. Proc. Natl Acad. Sci. U.S.A. 107:8346–8351, 2010.PubMedCentralPubMedCrossRefGoogle Scholar
- 21.Lencioni, R., T. de Baere, M. Burrel, J. G. Caridi, J. Lammer, K. Malagari, R. C. Martin, E. O’Grady, M. I. Real, T. J. Vogl, A. Watkinson, and J. F. Geschwind. Transcatheter treatment of hepatocellular carcinoma with doxorubicin-loaded DC bead (DEBDOX): technical recommendations. Cardiovasc. Interv. Radiol. 35:980–985, 2011.CrossRefGoogle Scholar
- 24.Lubbe, A. S., C. Bergemann, H. Riess, F. Schriever, P. Reichardt, K. Possinger, M. Matthias, B. Dorken, F. Herrmann, R. Gurtler, P. Hohenberger, N. Haas, R. Sohr, B. Sander, A. J. Lemke, D. Ohlendorf, W. Huhnt, and D. Huhn. Clinical experiences with magnetic drug targeting: a phase I study with 4′-epidoxorubicin in 14 patients with advanced solid tumors. Cancer Res. 56:4686–4693, 1996.PubMedGoogle Scholar
- 25.Martel, S. Combining pulsed and DC gradients in a clinical MRI-based microrobotic platform to guide therapeutic magnetic agents in the vascular network. Int. J. Robot. Res. 10:7, 2012.Google Scholar
- 26.Martel, S., O. Felfoul, J. B. Mathieu, A. Chanu, S. Tamaz, M. Mohammadi, M. Mankiewicz, and N. Tabatabaei. MRI-based medical nanorobotic platform for the control of magnetic nanoparticles and flagellated bacteria for target interventions in human capillaries. Int. J. Robot. Res. 28:1169–1182, 2009.CrossRefGoogle Scholar
- 27.Martel, S., J. B. Mathieu, O. Felfoul, A. Chanu, E. Aboussouan, S. Tamaz, P. Pouponneau, L. Yahia, G. Beaudoin, G. Soulez, and M. Mankiewicz. Automatic navigation of an untethered device in the artery of a living animal using a conventional clinical magnetic resonance imaging system. Appl. Phys. Lett. 90:114105, 2007.CrossRefGoogle Scholar
- 28.Martel, S., J. B. Mathieu, O. Felfoul, A. Chanu, E. Aboussouan, S. Tamaz, P. Pouponneau, L. Yahia, G. Beaudoin, G. Soulez, and M. Mankiewicz. A computer-assisted protocol for endovascular target interventions using a clinical MRI system for controlling untethered microdevices and future nanorobots. Comput. Aided Surg. 13:340–352, 2008.PubMedCrossRefGoogle Scholar
- 31.Namiki, Y., T. Namiki, H. Yoshida, Y. Ishii, A. Tsubota, S. Koido, K. Nariai, M. Mitsunaga, S. Yanagisawa, H. Kashiwagi, Y. Mabashi, Y. Yumoto, S. Hoshina, K. Fujise, and N. Tada. A novel magnetic crystal-lipid nanostructure for magnetically guided in vivo gene delivery. Nat. Nanotechnol. 4:598–606, 2009.PubMedCrossRefGoogle Scholar
- 35.Park, S., K. Cha, and J. Park. Development of biomedical microrobot for intravascular therapy. Int. J. Robot. Res. 7:97–98, 2010.Google Scholar
- 37.Polyak, B., I. Fishbein, M. Chorny, I. Alferiev, D. Williams, B. Yellen, G. Friedman, and R. J. Levy. High field gradient targeting of magnetic nanoparticle-loaded endothelial cells to the surfaces of steel stents. Proc. Natl Acad. Sci. U.S.A. 105:698–703, 2008.PubMedCentralPubMedCrossRefGoogle Scholar
- 40.Pouponneau, P., O. Savadogo, T. Napporn, L. Yahia, and S. Martel. Corrosion study of iron-cobalt alloys for MRI-based propulsion embedded in untethered microdevices operating in the vascular network. J. Biomed. Mater. Res. B 93:203–211, 2010.Google Scholar
- 43.Pouponneau, P., G. Soulez, G. Beaudoin, J. C. Leroux, and S. Martel. MR imaging of therapeutic magnetic microcarriers guided by magnetic resonance navigation for targeted liver chemoembolization. Cardiovasc. Interv. Radiol. DOI: 10.1007/s00270-013-0770-4, 2013.
- 44.Reyes, D. K., J. A. Vossen, I. R. Kamel, N. S. Azad, T. A. Wahlin, Torbenson, MS, M. A. Choti, and J. F. Geschwind. Single-center phase II trial of transarterial chemoembolization with drug-eluting beads for patients with unresectable hepatocellular carcinoma: initial experience in the United States. Cancer J. 15:526–532, 2009.PubMedCrossRefGoogle Scholar