Magnetic drug targeting: Preclinical in vivo studies, mathematical modeling, and extrapolation to humans

Al-Jamal, Khuloud T., Bai, Jie, Wang, Julie Tzu-Wen, Protti, Andrea, Southern, Paul, Bogart, Lara, Heidari, Hamed, Li, Xinjia, Cakebread, Andrew, Asker, Dan, Al-Jamal, Wafa T., Shah, Ajay, Bals, Sara, Sosabowski, Jane and Pankhurst, Quentin A. (2016) Magnetic drug targeting: Preclinical in vivo studies, mathematical modeling, and extrapolation to humans. Nano Letters, 16 (9). pp. 5652-5660. ISSN 1530-6984

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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.

Item Type: Article
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.
Uncontrolled Keywords: cancer therapy,nanomedicine,polymeric nanocapsules,spect imaging,superparamagnetic iron oxide nanoparticles
Faculty \ School: Faculty of Science > School of Pharmacy
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Depositing User: Pure Connector
Date Deposited: 05 Oct 2016 11:00
Last Modified: 22 Jul 2020 01:07
URI: https://ueaeprints.uea.ac.uk/id/eprint/60755
DOI: 10.1021/acs.nanolett.6b02261

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