Endoglin based in vivo near-infrared fluorescence imaging of tumor models in mice using activatable liposomes
| Autor: | Ingrid Hilger, Frank Steiniger, Ulf K. Teichgraeber, Ansgar M. Kollmeier, Alfred Fahr, Roland E. Kontermann, Markus Rabenhold, Ronny Rüger, Felista L. Tansi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Fluorescence-lifetime imaging microscopy Fibrosarcoma Biophysics Breast Neoplasms Biochemistry Fluorescence law.invention Mice 03 medical and health sciences 0302 clinical medicine In vivo Confocal microscopy law hemic and lymphatic diseases Tumor Cells Cultured otorhinolaryngologic diseases Animals Humans Molecular Biology Fluorescent Dyes Liposome Spectroscopy Near-Infrared Chemistry Optical Imaging Endoglin Xenograft Model Antitumor Assays In vitro 030104 developmental biology 030220 oncology & carcinogenesis Liposomes Drug delivery Cancer research Female Nanocarriers Single-Chain Antibodies |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - General Subjects. 1862:1389-1400 |
| ISSN: | 0304-4165 |
| DOI: | 10.1016/j.bbagen.2018.03.012 |
| Popis: | Background Endoglin (CD105) is overexpressed on tumor cells and tumor vasculatures, making it a potential target for diagnostic imaging and therapy of different neoplasms. Therefore, studies on nanocarrier systems designed for endoglin-directed diagnostic and drug delivery purposes would expose the feasibility of targeting endoglin with therapeutics. Methods Liposomes carrying high concentrations of a near-infrared fluorescent dye in the aqueous interior were prepared by the lipid film hydration and extrusion procedure, then conjugated to single chain antibody fragments either selective for murine endoglin (termed mEnd-IL) or directed towards human endoglin (termed hEnd-IL). A combination of Dynamic Light Scattering, electron microscopy, cell binding and uptake assays, confocal microscopy and in vivo fluorescence imaging of mice bearing xenografted human breast cancer and human fibrosarcoma models were implemented to elucidate the potentials of the liposomes. Results The mEnd-IL and hEnd-IL were highly selective for the respective murine- and human endoglin expressing cells in vitro and in vivo. Hence, the hEnd-IL bound distinctly to the tumor cells and enabled suitable fluorescence imaging of the tumors, whereas the mEnd-IL bound the tumor vasculature, but also to the liver, kidney and lung vasculature of mice. Conclusions The work highlights key differences between targeting vascular (murine) and neoplastic (human) endoglin in animal studies, and suggests that the hEnd-IL can serve as a delivery system that targets human endoglin overexpressed in pathological conditions. General significance The endoglin-targeting liposomes presented herewith represent strategic tools for the future implementation of endoglin-directed neoplastic and anti-angiogenic therapies. |
| Databáze: | OpenAIRE |
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