Abstract
Purpose
In this study, the contrasting properties of human serum albumin nanoparticles (HSA-NPs) loaded with gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and coated with transferrin in MRI in mice are evaluated.
Procedures
HSA-NPs were conjugated with Gd-DTPA (Gd-HSA-NPs) and coupled with transferrin (Gd-HSA-NP-Tf). Mice underwent MRI before or after injection of Gd-DTPA, Gd-HSA-NP, or Gd-HSA-NP-Tf.
Results
All the studied contrast agents provided a contrast enhancement (CE) in the blood, heart muscle, and liver. Compared to Gd-DTPA, CE with HSA-NP was achieved at lower Gd doses. Gd-HSA-NP-Tf yielded significantly higher CE than Gd-HSA-NP in the skeletal muscle, blood, cardiac muscle, and liver (p < 0.05). Gd-HSA-NP-Tf achieved a significantly higher CE than Gd-HSA-NP and Gd-DTPA in the blood, cardiac muscle, and liver (p < 0.05). In the brain, only Gd-HSA-NP-Tf was found to cause a significant CE (p < 0.05).
Conclusions
The Gd-HSA nanoparticles have potential as MRI contrast agents. In particular, Gd-HSA-NP-Tf has a potential as a specific contrast agent for the brain, while the blood–brain barrier is still intact, as well as in the heart, liver, and skeletal muscle.
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References
Suri SS, Fenniri H, Singh B (2007) Nanotechnology-based drug delivery systems. J Occup Med Toxicol 2:16
Anthony DC, Sibson NR, McAteer MA et al (2011) Detection of brain pathology by magnetic resonance imaging of iron oxide micro-particles. Methods Mol Biol 686:213–227
Enochs WS, Harsh G, Hochberg F, Weissleder R (1999) Improved delineation of human brain tumors on MR images using a long-circulating, superparamagnetic iron oxide agent. J Magn Reson Imaging 9:228–232
Kreuter J, Shamenkov D, Petrov V et al (2002) Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood–brain barrier. J Drug Target 10:317–325
Kreuter J (2001) Nanoparticulate systems for brain delivery of drugs. Adv Drug Deliv Rev 47:65–81
Ulbrich K, Hekmatara T, Herbert E, Kreuter J (2009) Transferrin- and transferrin-receptor-antibody-modified nanoparticles enable drug delivery across the blood–brain barrier (BBB). Eur J Pharm Biopharm 71:251–256
Kreuter J (2012) Mechanism of polymeric nanoparticle-based drug transport across the blood–brain barrier (BBB). Journal of Microencapsulation. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22676632. Accessed 7 June 2012
Ulbrich K, Knobloch T, Kreuter J (2011) Targeting the insulin receptor: nanoparticles for drug delivery across the blood–brain barrier (BBB). J Drug Target 19:125–132
Henrotte V, Muller RN, Bartholet A, Elst LV (2007) The presence of halide salts influences the non-covalent interaction of MRI contrast agents and human serum albumin. Contrast Media Mol Imaging 2:258–261
Weber C, Kreuter J, Langer K (2000) Desolvation process and surface characteristics of HSA-nanoparticles. Int J Pharm 196:197–200
Gouin S, Winnik FM (2001) Quantitative assays of the amount of diethylenetriaminepentaacetic acid conjugated to water-soluble polymers using isothermal titration calorimetry and colorimetry. Bioconjugate Chem 12:372–377
Heverhagen JT (2007) Noise measurement and estimation in MR imaging experiments. Radiology 245:638–639
National Electrical Manufacturers Association (2001) Determination of signal-to-noise ratio (SNR) in diagnostic magnetic resonance imaging. NEMA Standards Publication, Rosslyn, Virginia, MS 1-2001
Lewin M, Clement O, Belguise-Valladier P et al (2001) Hepatocyte targeting with Gd-EOB-DTPA: potential application for gene therapy. Invest Radiol 36:9–14
Mohs AM, Zong Y, Guo J et al (2005) PEG-g-poly(GdDTPA-co-L-cystine): effect of PEG chain length on in vivo contrast enhancement in MRI. Biomacromolecules 6:2305–11
Karfeld-Sulzer LS, Waters EA, Davis NE et al (2010) Multivalent protein polymer MRI contrast agents: controlling relaxivity via modulation of amino acid sequence. Biomacromolecules 11:1429–36
Glaus C, Rossin R, Welch MJ, Bao G (2010) In vivo evaluation of (64)Cu-labeled magnetic nanoparticles as a dual-modality PET/MR imaging agent. Bioconjug Chem 21:715–722
Oyewumi MO, Yokel RA, Jay M et al (2004) Comparison of cell uptake, biodistribution and tumor retention of folate-coated and PEG-coated gadolinium nanoparticles in tumor-bearing mice. J Control Release 95:613–626
Matsumura Y, Maeda H (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 46:6387–6392
Hesselink JR, Press GA (1988) MR contrast enhancement of intracranial lesions with Gd-DTPA. Radiol Clin North Am 26:873–887
Russell EJ, Schaible TF, Dillon W et al (1989) Multicenter double-blind placebo-controlled study of gadopentetate dimeglumine as an MR contrast agent: evaluation in patients with cerebral lesions. AJR Am J Roentgenol 152:813–823
Ichikawa H, Ishikawa M, Fukunaga M et al (2010) Quantitative evaluation of blood–cerebrospinal fluid barrier permeability in the rat with experimental meningitis using magnetic resonance imaging. Brain Res 1321:125–132
Visser CC, Stevanović S, Heleen Voorwinden L et al (2004) Validation of the transferrin receptor for drug targeting to brain capillary endothelial cells in vitro. J Drug Target 12:145–150
Hombach V, Merkle N, Bernhard P et al (2010) Prognostic significance of cardiac magnetic resonance imaging: update 2010. Cardiol J 17:549–557
Korkusuz H, Esters P, Huebner F et al (2010) Accuracy of cardiovascular magnetic resonance in myocarditis: comparison of MR and histological findings in an animal model. J Cardiovasc Magn Reson 12:49
Gulyaev AE, Gelperina SE, Skidan IN et al (1999) Significant transport of doxorubicin into the brain with polysorbate 80-coated nanoparticles. Pharm Res 16:1564–9
Beitzke D, Wolf F, Edelhauser G et al (2010) Right heart dilatation in adult congenital heart disease: imaging appearance on cardiac magnetic resonance. Br J Radiol 84:188–93
Oudit GY, Trivieri MG, Khaper N et al (2006) Role of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy. J Mol Med 84:349–364
Acknowledgments
This work was supported by grants from the Wilhelm Sander Stiftung (2003.119.2), the Else Kröner-Fresenius Stiftung, the Deutsche Forschungsgemeinschaft (GRK 1172), and the Heinrich und Erna Schaufler-Stiftung.
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The authors declare that they have no conflict of interest.
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Karsten Ulbrich, Katerina Welzel, and Verena Koeberle contributed equally to this work.
Joerg Kreuter, Thomas J. Vogl, and Albrecht Piiper shared senior authorship.
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Korkusuz, H., Ulbrich, K., Welzel, K. et al. Transferrin-Coated Gadolinium Nanoparticles as MRI Contrast Agent. Mol Imaging Biol 15, 148–154 (2013). https://doi.org/10.1007/s11307-012-0579-6
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DOI: https://doi.org/10.1007/s11307-012-0579-6