Detecting Chronic Post-Traumatic Osteomyelitis of Mouse Tibia via an IL-13Rα2 Targeted Metallofullerene Magnetic Resonance Imaging Probe.
Detecting Chronic Post-Traumatic Osteomyelitis of Mouse Tibia via an IL-13Rα2 Targeted Metallofullerene Magnetic Resonance Imaging Probe.
复制标题
DOI：
10.1021/acs.bioconjchem.6b00708
复制
发表时间：
2017-02-15
影响因子：
4.7
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Xiao L;Li T;Ding M;Yang J;Rodríguez-Corrales J;LaConte SM;Nacey N;Weiss DB;Jin L;Dorn HC;Li X
慢性创伤后骨髓炎（CPO）与无菌性炎症的鉴别诊断仍然具有挑战性，因为两种病理过程具有相似的临床症状。在这里，我们使用了一种新的靶向金属富勒烯纳米颗粒为基础的磁共振成像（MRI）探针IL-13-TAMRA-Gd 3 N @C80（OH）30−（CH 2CH 2COOH）20通过过表达的IL-13 R α2受体检测小鼠胫骨中的CPO。功能化的金属富勒烯，其特征在于通过X射线光电子能谱。脂多糖（LPS）刺激后，巨噬细胞Raw 264.7细胞通过免疫荧光染色显示IL-13 R α2表达升高，通过内置塔姆拉荧光成像显示MRI探针结合增加。在小鼠的两个胫骨中诱导创伤，并将细菌浸泡的缝线插入右侧胫骨中以引发感染。在急性期（1.5周），鲁米诺生物发光成像显示，与假手术组相比，感染胫骨中的髓过氧化物酶活性要高得多。在慢性期（4周），X线摄影显示与假手术组相比，感染胫骨中的骨变形。在T1加权序列中，在急性期和慢性期，探头在感染灶中均明显显示高信号，而在假手术胫骨中未观察到。组织学分析显示，严重的骨结构破坏和大量炎症细胞浸润的感染胫骨。免疫组化证实感染部位IL-13 R α2表达丰富。总之，我们开发了一种非侵入性成像方法，使用新的IL-13 R α2靶向金属富勒烯MRI探针检测和区分CPO和无菌性炎症。此外，首次将IL-13 R α2作为骨髓炎背景下的独特生物标志物进行了研究。我们的数据建立了一个基础的翻译应用程序的MRI探头在临床上的CPO的鉴别。
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.