Adhesion molecule–targeted magnetic particle imaging nanoprobe for visualization of inflammation in acute lung injury
Purpose Uncontrolled intra-alveolar inflammation is a central pathogenic feature, and its severity translates into a valid prognostic indicator of acute lung injury (ALI). Unfortunately, current clinical imaging approaches are unsuitable for visualizing and quantifying intra-alveolar inflammation. This study aimed to construct a small-sized vascular cell adhesion molecule-1 (VCAM-1)-targeted magnetic particle imaging (MPI) nanoprobe (ESPVPN) to visualize and accurately quantify intra-alveolar inflammation at the molecular level. Methods ESPVPN was engineered by conjugating a peptide (VHPKQHRGGSK(Cy7)GC) onto a polydopamine-functionalized superparamagnetic iron oxide core. The MPI performance, targeting, and biosafety of the ESPVPN were characterized. VCAM-1 expression in HUVECs and mouse models was evaluated by western blot. The degree of inflammation and distribution of VCAM-1 in the lungs were assessed using histopathology. The expression of pro-inflammatory markers and VCAM-1 in lung tissue lysates was measured using ELISA. After intravenous administration of ESPVPN, MPI and CT imaging were used to analyze the distribution of ESPVPN in the lungs of the LPS-induced ALI models. Results The small-sized (~10 nm) ESPVPN exhibited superior MPI performance compared to commercial $ MagImaging^{®} $ and Vivotrax, and ESPVPN had effective targeting and biosafety. VCAM-1 was highly expressed in LPS-induced ALI mice. VCAM-1 expression was positively correlated with the LPS-induced dose (R = 0.9381). The in vivo MPI signal showed positive correlations with both VCAM-1 expression (R = 0.9186) and representative pro-inflammatory markers (MPO, TNF-α, IL-6, IL-8, and IL-1β, R > 0.7). Conclusion ESPVPN effectively targeted inflammatory lungs and combined the advantages of MPI quantitative imaging to visualize and evaluate the degree of ALI inflammation..
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:51 |
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Enthalten in: |
European journal of nuclear medicine and molecular imaging - 51(2023), 5 vom: 14. Dez., Seite 1233-1245 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Gao, Pengli [VerfasserIn] |
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Links: |
Volltext [lizenzpflichtig] |
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Themen: |
Acute lung injury |
Anmerkungen: |
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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doi: |
10.1007/s00259-023-06550-4 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
SPR055233929 |
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520 | |a Purpose Uncontrolled intra-alveolar inflammation is a central pathogenic feature, and its severity translates into a valid prognostic indicator of acute lung injury (ALI). Unfortunately, current clinical imaging approaches are unsuitable for visualizing and quantifying intra-alveolar inflammation. This study aimed to construct a small-sized vascular cell adhesion molecule-1 (VCAM-1)-targeted magnetic particle imaging (MPI) nanoprobe (ESPVPN) to visualize and accurately quantify intra-alveolar inflammation at the molecular level. Methods ESPVPN was engineered by conjugating a peptide (VHPKQHRGGSK(Cy7)GC) onto a polydopamine-functionalized superparamagnetic iron oxide core. The MPI performance, targeting, and biosafety of the ESPVPN were characterized. VCAM-1 expression in HUVECs and mouse models was evaluated by western blot. The degree of inflammation and distribution of VCAM-1 in the lungs were assessed using histopathology. The expression of pro-inflammatory markers and VCAM-1 in lung tissue lysates was measured using ELISA. After intravenous administration of ESPVPN, MPI and CT imaging were used to analyze the distribution of ESPVPN in the lungs of the LPS-induced ALI models. Results The small-sized (~10 nm) ESPVPN exhibited superior MPI performance compared to commercial $ MagImaging^{®} $ and Vivotrax, and ESPVPN had effective targeting and biosafety. VCAM-1 was highly expressed in LPS-induced ALI mice. VCAM-1 expression was positively correlated with the LPS-induced dose (R = 0.9381). The in vivo MPI signal showed positive correlations with both VCAM-1 expression (R = 0.9186) and representative pro-inflammatory markers (MPO, TNF-α, IL-6, IL-8, and IL-1β, R > 0.7). Conclusion ESPVPN effectively targeted inflammatory lungs and combined the advantages of MPI quantitative imaging to visualize and evaluate the degree of ALI inflammation. | ||
650 | 4 | |a Acute lung injury |7 (dpeaa)DE-He213 | |
650 | 4 | |a Inflammation |7 (dpeaa)DE-He213 | |
650 | 4 | |a Vascular cell adhesion molecule-1 |7 (dpeaa)DE-He213 | |
650 | 4 | |a Magnetic particle imaging |7 (dpeaa)DE-He213 | |
700 | 1 | |a Liu, Yu |4 aut | |
700 | 1 | |a Wang, Xiaoli |4 aut | |
700 | 1 | |a Feng, Xin |4 aut | |
700 | 1 | |a Liu, Heng |4 aut | |
700 | 1 | |a Liu, Songlu |4 aut | |
700 | 1 | |a Huang, Xiazi |4 aut | |
700 | 1 | |a Wu, Xiangjun |4 aut | |
700 | 1 | |a Xiong, Fei |4 aut | |
700 | 1 | |a Jia, Xiaohua |4 aut | |
700 | 1 | |a Hui, Hui |4 aut | |
700 | 1 | |a Jiang, Jingying |4 aut | |
700 | 1 | |a Tian, Jie |0 (orcid)0000-0003-0498-0432 |4 aut | |
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