Non-Invasive Detection of Lung Inflammation by Near-Infrared Fluorescence Imaging Using Bimodal Liposomes

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• 作者：Hari R. Desu ; George C. Wood ; Laura A. Thoma
• 关键词：Acute lung injury ; Diagnostic ; Fluorescence ; Imaging ; Liposome ; Targeting
• 刊名：Journal of Fluorescence
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：26
• 期：1
• 页码：241-253
• 全文大小：1,469 KB
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• 作者单位：Hari R. Desu (1)
  George C. Wood (2)
  Laura A. Thoma (3)
  
  1. Pharmaceutical Consultancy Services, Hyderabad, India
  2. Department of Pharmaceutical Sciences, The University of Tennessee Health Science Center, Memphis, TN, USA
  3. College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN, USA
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Biomedicine
  Biophysics and Biomedical Physics
  Biotechnology
  Biochemistry
  Analytical Chemistry
  
• 出版者：Springer Netherlands
• ISSN：1573-4994

文摘

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome results in respiratory obstruction and severe lung inflammation. Critical characteristics of ALI are alveolar edema, infiltration of leukocytes (neutrophils and monocytes), release of pro-inflammatory cytokines and chemokines into broncho-alveolar lavage fluid, and activation of integrin receptors. The purpose of the study was to demonstrate non-invasive detection of lung inflammation using integrin receptor targeted fluorescence liposomes. An inflammation similar to that observed in ALI was elicited in rodents by intra-tracheal instillation of interleukin-1beta (IL-1beta). Cyclic arginine glycine-(D)-aspartic acid-peptide (cRGD-peptide) grafted fluorescence liposomes were administered to ALI induced male Sprague-Dawley rats for targeting lung integrin receptors. Near-infrared fluorescence imaging (NIRFI) was applied for visualization and quantitation of lung inflammation. NIRFI signals were correlated with inflammatory cellular and biochemical markers of lungs. A positive correlation was observed between NIRF signals and lung inflammation markers. Compared to control group, an intense NIRF signal was observed in ALI induced rats in the window 6–24 h post-IL-1beta instillation. Interaction of integrin receptors with targeted liposomes was assumed to contribute to intense NIRF signal. RT-PCR studies showed an elevated lung expression of alphavbeta5 integrin receptors, 12 h post-IL-1beta instillation. In vitro studies demonstrated integrin receptor specificity of targeted liposomes. These targeted liposomes showed binding to alphavbeta5 integrin receptors expressed on alveolar cells. Non-invasive detection of lung inflammation was demonstrated using a combination of integrin receptor targeting and NIRFI. Keywords Acute lung injury Diagnostic Fluorescence Imaging Liposome Targeting