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“Magnetic drug targeting : preclinical in vivo studies, mathematical modeling, and extrapolation to humans”. Al-Jamal KT, Bai J, Wang JTW, Protti A, Southern P, Bogart L, Heidari H, Li X, Cakebread A, Asker D, Al-Jamal WT, Shah A, Bals S, Sosabowski J, Pankhurst QA;, Nano letters 16, 5652 (2016). http://doi.org/10.1021/ACS.NANOLETT.6B02261
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 nano carriers, 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.
Keywords: A1 Journal article; Engineering sciences. Technology; Electron microscopy for materials research (EMAT)
Impact Factor: 12.712
Times cited: 128
DOI: 10.1021/ACS.NANOLETT.6B02261
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“Magnetically decorated multiwalled carbon nanotubes as dual MRI and SPECT contrast agents”. Wang JTW, Cabana L, Bourgognon M, Kafa H, Protti A, Venner K, Shah AM, Sosabowski JK, Mather SJ, Roig A, Ke X, Van Tendeloo G, de Rosales RTM, Tobias G, Al-Jamal KT, Advanced functional materials 24, 1880 (2014). http://doi.org/10.1002/adfm.201302892
Abstract: Carbon nanotubes (CNTs) are one of the most promising nanomaterials to be used in biomedicine for drug/gene delivery as well as biomedical imaging. This study develops radio-labeled, iron oxide-decorated multiwalled CNTs (MWNTs) as dual magnetic resonance (MR) and single photon emission computed tomography (SPECT) contrast agents. Hybrids containing different amounts of iron oxide are synthesized by in situ generation. Physicochemical characterisations reveal the presence of superparamagnetic iron oxide nanoparticles (SPION) granted the magnetic properties of the hybrids. Further comprehensive examinations including high resolution transmission electron microscopy (HRTEM), fast Fourier transform simulations, X-ray diffraction, and X-ray photoelectron spectroscopy assure the conformation of prepared SPION as γ-Fe2O3. High r2 relaxivities are obtained in both phantom and in vivo MRI compared to the clinically approved SPION Endorem. The hybrids are successfully radio labeled with technetium-99m through a functionalized bisphosphonate and enable SPECT/CT imaging and γ-scintigraphy to quantitatively analyze the biodistribution in mice. No abnormality is found by histological examination and the presence of SPION and MWNT are identified by Perls stain and Neutral Red stain, respectively. TEM images of liver and spleen tissues show the co-localization of SPION and MWNTs within the same intracellular vesicles, indicating the in vivo stability of the hybrids after intravenous injection. The results demonstrate the capability of the present SPIONMWNT hybrids as dual MRI and SPECT contrast agents for in vivo use.
Keywords: A1 Journal article; Engineering sciences. Technology; Electron microscopy for materials research (EMAT)
Impact Factor: 12.124
Times cited: 50
DOI: 10.1002/adfm.201302892
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“Triple-Modal Imaging of Magnetically-Targeted Nanocapsules in Solid TumoursIn Vivo”. Bai J, Wang JT-W, Rubio N, Protti A, Heidari H, Elgogary R, Southern P, Al-Jamal W' T, Sosabowski J, Shah AM, Bals S, Pankhurst QA, Al-Jamal KT, Theranostics 6, 342 (2016). http://doi.org/10.7150/thno.11918
Abstract: Triple-modal imaging magnetic nanocapsules, encapsulating hydrophobic superparamagnetic iron oxide nanoparticles, are formulated and used to magnetically target solid tumours after intravenous administration in tumour-bearing mice. The engineered magnetic polymeric nanocapsules m-NCs are ~200 nm in size with negative Zeta potential and shown to be spherical in shape. The loading efficiency of superparamagnetic iron oxide nanoparticles in the m-NC was ~100%. Up to ~3- and ~2.2-fold increase in tumour uptake at 1 and 24 h was achieved, when a static magnetic field was applied to the tumour for 1 hour. m-NCs, with multiple imaging probes (e.g. indocyanine green, superparamagnetic iron oxide nanoparticles and indium-111), were capable of triple-modal imaging (fluorescence/magnetic resonance/nuclear imaging) in vivo. Using triple-modal imaging is to overcome the intrinsic limitations of single modality imaging and provides complementary information on the spatial distribution of the nanocarrier within the tumour. The significant findings of this study could open up new research perspectives in using novel magnetically-responsive nanomaterials in magnetic-drug targeting combined with multi-modal imaging.
Keywords: A1 Journal article; Electron microscopy for materials research (EMAT)
Impact Factor: 8.712
Times cited: 54
DOI: 10.7150/thno.11918
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“Engineering hepatitis B virus core particles for targeting HER2 receptors in vitro and in vivo”. Suffian IFBM, Wang JT-W, Hodgins NO, Klippstein R, Garcia-Maya M, Brown P, Nishimura Y, Heidari H, Bals S, Sosabowski JK, Ogino C, Kondo A, Al-Jamal KT, Biomaterials 120, 126 (2017). http://doi.org/10.1016/J.BIOMATERIALS.2016.12.012
Abstract: Hepatitis B Virus core (HBc) particles have been studied for their potential as drug delivery vehicles for cancer therapy. HBc particles are hollow nano-particles of 30-34 nm diameter and 7 nm thick envelopes, consisting of 180-240 units of 21 kDa core monomers. They have the capacity to assemble/dis-assemble in a controlled manner allowing encapsulation of various drugs and other biomolecules. Moreover, other functional motifs, i.e. receptors, receptor binding sequences, peptides and proteins can be expressed. This study focuses on the development of genetically modified HBc particles to specifically recognise and target human epidermal growth factor receptor-2 (HER2)-expressing cancer cells, in vitro and in vivo, for future cancer therapy. The non-specific binding capacity of wild type HBc particles was reduced by genetic deletion of the sequence encoding arginine-rich domains. A specific HER2-targeting was achieved by expressing the ZHER2 affibodies on the HBc particles surface. In vitro studies showed specific uptake of ZHER2-AHBc particles in HER2 expressing cancer cells. In vivo studies confirmed positive uptake of ZHER2-ABBc particles in HER2-expressing tumours, compared to non-targeted AHBc particles in intraperitoneal tumour-bearing mice models. The present results highlight the potential of these nanocarriers in targeting HER2-positive metastatic abdominal cancer following intra-peritoneal administration. (C) 2016 The Authors. Published by Elsevier Ltd.
Keywords: A1 Journal article; Electron microscopy for materials research (EMAT)
Impact Factor: 8.402
Times cited: 20
DOI: 10.1016/J.BIOMATERIALS.2016.12.012
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