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Assessment of the targeting specificity of fluorescent albumin conceived as a preclinical agent of the liver function

Abstract

In the context of increasing liver diseases, no contrast agent is currently available in Europe and united states to directly assess the liver function. Sole, neolactosylated human serum albumin is being clinically used in Asia. In order to perform preclinical studies in the context of liver diseases, we conceived a fluorescent lactosylated albumin for the quantification of the liver functional cells (L-Cyal). A precise characterization was achieved in order to determine the amount of lactose and Cyanine 5 (Cy5) coupled to albumin. In addition, potential aggregation was characterized by asymmetrical flow field-flow fractionation hyphenated to multi-angle light scattering (AF4-MALS). The optimal functionalized albumin exhibited a mass superior to 87 kDa which corresponds to the addition of 34 lactose moieties per protein and 1-2 Cy5 labels. Also, no significant formation of aggregates could be identified due to the modification of native albumin. In healthy mice, liver accumulation of L-Cyal and its selectivity for hepatocyte cells was shown by optical imaging and flow cytometry. Administration of L-Cyal to a mice bearing liver metastases showed a reduced signal in the liver related to a decrease number of hepatocytes. The L-CyaL bioimaging contrast agent can be particular useful for assessing the state of liver related diseases.

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Publication details

The article was received on 23 May 2018, accepted on 03 Oct 2018 and first published on 05 Oct 2018


Article type: Paper
DOI: 10.1039/C8NR04163F
Citation: Nanoscale, 2018, Accepted Manuscript
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    Assessment of the targeting specificity of fluorescent albumin conceived as a preclinical agent of the liver function

    K. Lemdani, H. Salmon, R. Gahoual, M. Bessodes, D. Scherman, P. Houzé, J. Seguin and N. Mignet, Nanoscale, 2018, Accepted Manuscript , DOI: 10.1039/C8NR04163F

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