Efficient CRM197-mediated drug targeting to monocytes

Efficient delivery of drugs to specific cellular reservoirs is of particular importance for therapeutics that are not able to pass cellular barriers and that may have unwanted side effects in off-target tissues. Heparin-binding epidermal growth factor (HB-EGF) is expressed on leukocytes and may be t...

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Bibliographic Details
Published in:Journal of controlled release 2012-02, Vol.158 (1), p.139-147
Main Authors: Schenk, Geert J., Haasnoot, P.C. Joost, Centlivre, Mireille, Legrand, Nicolas, Rip, Jaap, de Boer, Albertus G., Berkhout, Ben
Format: Article
Language:English
Subjects:
Animals
Bacterial Proteins - administration & dosage
Biological and medical sciences
Cell Line
Cricetinae
CRM197
DNA-Binding Proteins - deficiency
DNA-Binding Proteins - genetics
Drug Delivery Systems
Drug targeting
Female
General pharmacology
HB-EGF
Heparin-binding EGF-like Growth Factor
Human immune system mouse
Humans
Intercellular Signaling Peptides and Proteins - metabolism
Interleukin Receptor Common gamma Subunit - deficiency
Interleukin Receptor Common gamma Subunit - genetics
Liposomes
Medical sciences
Mice
Mice, Knockout
Monocytes
Monocytes - metabolism
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
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Summary:Efficient delivery of drugs to specific cellular reservoirs is of particular importance for therapeutics that are not able to pass cellular barriers and that may have unwanted side effects in off-target tissues. Heparin-binding epidermal growth factor (HB-EGF) is expressed on leukocytes and may be targeted for specific drug delivery using cross-reacting material (CRM)197, a non-toxic variant of diphtheria toxin and exogenous substrate for HB-EGF. We used fluorescently labeled CRM197 and CRM197-coated liposomes to investigate their potential use for drug delivery to leukocytes. We demonstrate that CRM197-guided systems are efficiently taken up by human leukocytes in vitro. CRM197 was also found to specifically target leukocytes in vivo in mice with components of the human immune system (HIS mice) and hamsters. Monocytes represent the most prominent subset of leukocytes that showed highly specific CRM197-mediated uptake. We therefore propose the application of CRM197 as a novel targeting approach in diseases that require the selective treatment of monocytes. [Display omitted]
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2011.09.091