Detecting Chronic Post-Traumatic Osteomyelitis of Mouse Tibia via an IL-13Rα2 Targeted Metallofullerene Magnetic Resonance Imaging Probe

Autor: José Á. Rodríguez-Corrales, Harry C. Dorn, Stephen M. LaConte, Mengmeng Ding, Li Xiao, Li Jin, Nicholas Nacey, Xudong Li, David B. Weiss, Jiezuan Yang, Tinghui Li
Rok vydání: 2017
Předmět:
Models
Molecular
0301 basic medicine
Fluorescence-lifetime imaging microscopy
Pathology
medicine.medical_specialty
Lipopolysaccharide
Biomedical Engineering
Pharmaceutical Science
Gadolinium
Bioengineering
Stimulation
02 engineering and technology
Article
Mice
03 medical and health sciences
chemistry.chemical_compound
medicine
Animals
Amino Acid Sequence
Tibia
Receptor
Pharmacology
Mice
Inbred BALB C
Interleukin-13
medicine.diagnostic_test
Osteomyelitis
Receptors
Interleukin-13
Organic Chemistry
Magnetic resonance imaging
021001 nanoscience & nanotechnology
medicine.disease
Magnetic Resonance Imaging
RAW 264.7 Cells
030104 developmental biology
chemistry
Chronic Disease
Metallofullerene
Interleukin-13 Receptor alpha2 Subunit
Nanoparticles
Female
Fullerenes
0210 nano-technology
Biomarkers
Biotechnology
Zdroj: Bioconjugate Chemistry. 28:649-658
ISSN: 1520-4812
1043-1802
Popis: Differential diagnosis of chronic post-traumatic osteomyelitis (CPO) from aseptic inflammation remains challenging, since both pathological processes share similar clinical symptoms. Here we utilized a novel targeted metallofullerene nanoparticle based magnetic resonance imaging (MRI) probe IL-13-TAMRA-Gd3N@C80(OH)30− (CH2CH2COOH)20 to detect CPO in mouse tibia via overexpressed IL-13Rα2 receptors. The functionalized metallofullerene was characterized by X-ray photoelectron spectroscopy. Upon lipopolysaccharide (LPS) stimulation, macrophage Raw 264.7 cells showed elevated IL-13Rα2 expression via immunofluorescence staining and increased MRI probe binding via built-in TAMRA fluorescence imaging. Trauma was induced in both tibia of mice and bacteria soaked suture was inserted into the right tibia to initiate infection. During the acute phase (1.5 weeks), luminol-bioluminescence imaging revealed much higher myeloperoxidase activity in the infected tibia compared to the sham. In the chronic phase (4 weeks), X-ray radiography illustrated bone deformation in the infected tibia compared to the sham. With T1 weighted sequences, the probe clearly exhibited hyperintensity in the infection foci at both acute and chronic phases, which was not observed in the sham tibia. Histological analysis revealed severe bone structural destruction and massive inflammatory cell infiltration in the infected tibia. Immunohistochemistry confirmed abundant expression of IL-13Rα2 in the infection site. In summary, we developed a noninvasive imaging approach to detect and differentiate CPO from aseptic inflammation using a new IL-13Rα2 targeted metallofullerene MRI probe. In addition, for the first time, IL-13Rα2 was investigated as a unique biomarker in the context of osteomyelitis. Our data established a foundation for the translational application of this MRI probe in the clinical differentiation of CPO.
Databáze: OpenAIRE
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