title: Specific targeting and noninvasive magnetic resonance imaging of an asthma biomarker in the lung using polyethylene glycol functionalized magnetic nanocarriers.
abstract: Simultaneous inhibition of IL4 and IL13 via the common receptor chain IL4Rα to block adequately their biologic effects presents a promising therapeutic approach to give the additional relief required for asthma patients. In this study, superparamagnetic iron oxide nanoparticles were conjugated with anti-IL4Rα blocking antibodies via polyethylene glycol (PEG) polymers. The delivery of these blocking antibodies to the inflammatory sites in the lung via the developed nanocarriers was assessed using noninvasive free-breathing pulmonary MRI. Biocompatibility assays confirmed the safety of the developed nanocarriers for pre-clinical investigations. For all the investigated formulations, nanocarriers were found to be very stable at neutral pH. However, the stability noticeably decreased with the PEG length in acidic environment and thus the loaded antibodies were preferentially released. Immunofluorescence and fluorimetry assays confirmed the binding of the nanocarriers to the IL4Rα asthma biomarker. Pulmonary MRI performed using an ultra-short echo time sequence allowed simultaneous noninvasive monitoring of inflammatory responses induced by ovalbumin challenge and tracking of the developed nanocarriers, which were found to colocalize with the inflammatory sites in the lung. Targeting of the developed nanocarriers to areas rich in IL4Rα positive inflammatory cells was confirmed using histological and flow cytometry analyses. The anti-IL4Rα-conjugated nanocarriers developed here have been confirmed to be efficient in targeting key inflammatory cells during chronic lung inflammation following intrapulmonary administration. Targeting efficiency was monitored using noninvasive MRI, allowing detection of the nanocarriers' colocalizations with the inflammatory sites in the lung of ovalbumin-challenged asthmatic mice. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: King Saud University, Department of Radiological Sciences, College of Applied Medical Sciences, Riyadh, Saudi Arabia.
authors.forename: Achraf
authors.initials: A
authors.lastname: Al Faraj
authors.affiliation: King Saud University, Prince Naif Health Research Center, Riyadh, Saudi Arabia.|King Saud University, Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, Riyadh, Saudi Arabia.
authors.forename: Asma Sultana
authors.initials: AS
authors.lastname: Shaik
authors.affiliation: King Saud University, Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, Riyadh, Saudi Arabia.
authors.forename: Sibtain
authors.initials: S
authors.lastname: Afzal
authors.affiliation: King Saud University, Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, Riyadh, Saudi Arabia.
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Muhsen
authors.affiliation: King Saud University, Prince Naif Center for Immunology Research and Asthma Research Chair, Department of Pediatrics, College of Medicine, Riyadh, Saudi Arabia.
authors.forename: Rabih
authors.initials: R
authors.lastname: Halwani
mesh_terms: D000818:Animals; D001249:Asthma / Q000000981:diagnostic imaging* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D018796:Immunoconjugates / Q000737:chemistry; D007249:Inflammation / Q000000981:diagnostic imaging; D007518:Isoantibodies / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000000981:diagnostic imaging* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging / Q000379:methods*; D011092:Polyethylene Glycols; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D015415:Biomarkers; D004337:Drug Carriers; D018796:Immunoconjugates; D007518:Isoantibodies; D058185:Magnetite Nanoparticles; D011092:Polyethylene Glycols; D011956:Receptors, Cell Surface; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit
keywords: asthma biomarkers; lung imaging; magnetic resonance imaging; specific targeting; superparamagnetic iron oxide nanoparticles