This study aimed to improve the targeting of superparamagnetic iron oxide nanoparticles (SPIONs) to the lung after intravenous administration. In order to achieve a higher pulmonary delivery, high-energy flexible magnets were optimized and externally applied to a specific region of mouse lung. SPIONs and magnets were first characterized, and a free-breathing magnetic resonance imaging (MRI) protocol was then optimized to allow noninvasive monitoring and for their sensitive detection to the target site in the lung, using an ultrashort time of echo radial MR pulse sequence. In addition, histological analysis using Perls’ staining and iron quantification using inductive couple plasma-mass spectroscopy (ICP-MS) were performed to confirm MRI readouts. A flexible magnet with inverse multiple polarities was found to enhance the magnetic targeting of SPIONs to the lung. MRI readouts enabled successful detection of enhanced SPION migration to the lower right lobe, where the magnet was positioned. Attracted by the magnet, SPIONs were found to accumulate in the lung tissue within 2 h post-injection as seen in histological images and through ICP-MS, where a notable increase in iron concentrations were observed in the magnet group compared to control mice. In conclusion, the external application of an optimized high-energy magnet with multiple polarities over specific regions of the lung enhanced the magnetic targeting of SPIONs to the site of interest within the lung after intravenous injection.
Magnetic resonance imaging Magnetic targeting Superparamagnetic iron oxide nanoparticles Lung Noninvasive imaging Nanomedicine
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This work was supported by NSTIP strategic technologies programs, No. (12-MED2536), in the Kingdom of Saudi Arabia. The authors thank Saud Alotaibi for his help in the experimental procedures, Khaled Shamma and Syed Atif Ali for their help in ICP-MS measurements, Arkadi Vernikov from Vernikov magnet for magnet’s design, and Koen Vervaeke and Luc Van de Perre from MagCam for magnet’s characterization.
Al Faraj A, Shaik AS, Afzal S, Al Sayed B, Halwani R (2014a) MR imaging and targeting of a specific alveolar macrophage subpopulation in LPS-induced COPD animal model using antibody-conjugated magnetic nanoparticles. Int J Nanomedicine 9:1491–1503. doi:10.2147/IJN.S59394CrossRefGoogle Scholar
Al Faraj A, Sultana Shaik A, Pureza MA, Alnafea M, Halwani R (2014b) Preferential macrophage recruitment and polarization in LPS-induced animal model for COPD: noninvasive tracking using MRI. PLoS One 9:e90829. doi:10.1371/journal.pone.0090829CrossRefGoogle Scholar
Alexiou C et al (2000) Locoregional cancer treatment with magnetic drug targeting. Cancer Res 60:6641–6648Google Scholar
Grüttner C, Müller K, Teller J, Westphal F, Foreman A, Ivkov R (2007) Synthesis and antibody conjugation of magnetic nanoparticles with improved specific power absorption rates for alternating magnetic field cancer therapy. J Magn Magn Mater 311:181–186. doi:10.1016/j.jmmm.2006.10.1151CrossRefGoogle Scholar
Rohrer M, Bauer H, Mintorovitch J, Requardt M, Weinmann HJ (2005) Comparison of magnetic properties of MRI contrast media solutions at different magnetic field strengths. Invest Radiol 40:715–724CrossRefGoogle Scholar
Sensenig R, Sapir Y, MacDonald C, Cohen S, Polyak B (2012) Magnetic nanoparticle-based approaches to locally target therapy and enhance tissue regeneration in vivo. Nanomedicine (Lond) 7:1425–1442. doi:10.2217/nnm.12.109CrossRefGoogle Scholar
Widder KJ, Morris RM, Poore G, Howard DP Jr, Senyei AE (1981) Tumor remission in Yoshida sarcoma-bearing rts by selective targeting of magnetic albumin microspheres containing doxorubicin. Proc Natl Acad Sci USA 78:579–581CrossRefGoogle Scholar