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Magnetic Drug Targeting: Preclinical in Vivo Studies, Mathematical Modeling, and Extrapolation to Humans

Al-Jamal, KT; Bai, J; Wang, JT-W; Protti, A; Southern, P; Bogart, L; Heidari, H; ... Pankhurst, QA; + view all (2016) Magnetic Drug Targeting: Preclinical in Vivo Studies, Mathematical Modeling, and Extrapolation to Humans. Nano Letters , 16 (9) pp. 5652-5660. 10.1021/acs.nanolett.6b02261. Green open access

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Abstract

A sound theoretical rationale for the design of a magnetic nanocarrier capable of magnetic capture in vivo after intravenous administration could help elucidate the parameters necessary for in vivo magnetic tumor targeting. In this work, we utilized our long-circulating polymeric magnetic nanocarriers, encapsulating increasing amounts of superparamagnetic iron oxide nanoparticles (SPIONs) in a biocompatible oil carrier, to study the effects of SPION loading and of applied magnetic field strength on magnetic tumor targeting in CT26 tumor-bearing mice. Under controlled conditions, the in vivo magnetic targeting was quantified and found to be directly proportional to SPION loading and magnetic field strength. Highest SPION loading, however, resulted in a reduced blood circulation time and a plateauing of the magnetic targeting. Mathematical modeling was undertaken to compute the in vivo magnetic, viscoelastic, convective, and diffusive forces acting on the nanocapsules (NCs) in accordance with the Nacev–Shapiro construct, and this was then used to extrapolate to the expected behavior in humans. The model predicted that in the latter case, the NCs and magnetic forces applied here would have been sufficient to achieve successful targeting in humans. Lastly, an in vivo murine tumor growth delay study was performed using docetaxel (DTX)-encapsulated NCs. Magnetic targeting was found to offer enhanced therapeutic efficacy and improve mice survival compared to passive targeting at drug doses of ca. 5–8 mg of DTX/kg. This is, to our knowledge, the first study that truly bridges the gap between preclinical experiments and clinical translation in the field of magnetic drug targeting.

Type: Article
Title: Magnetic Drug Targeting: Preclinical in Vivo Studies, Mathematical Modeling, and Extrapolation to Humans
Open access status: An open access version is available from UCL Discovery
DOI: 10.1021/acs.nanolett.6b02261
Publisher version: http://dx.doi.org/10.1021/acs.nanolett.6b02261
Language: English
Additional information: This is an open access article published under an ACS AuthorChoice License , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
Keywords: Science & Technology, Physical Sciences, Technology, Chemistry, Multidisciplinary, Chemistry, Physical, Nanoscience & Nanotechnology, Materials Science, Multidisciplinary, Physics, Applied, Physics, Condensed Matter, Chemistry, Science & Technology - Other Topics, Materials Science, Physics, Polymeric Nanocapsules, Superparamagnetic Iron Oxide Nanoparticles, Spelt Imaging, Cancer Therapy, Nanomedicine, Iron-Oxide Nanoparticles, Cancer-Therapy, Solid Tumors, Delivery, Hydrodynamics, Nanocapsules, Blood, Field
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Chemical Engineering
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng
URI: https://discovery.ucl.ac.uk/id/eprint/1508641
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