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Efficient CRM197-mediated drug targeting to monocytes

Authors
Journal
Journal of Controlled Release
0168-3659
Publisher
Elsevier
Publication Date
Volume
158
Issue
1
Identifiers
DOI: 10.1016/j.jconrel.2011.09.091
Keywords
  • Hb-Egf
  • Crm197
  • Monocytes
  • Drug Targeting
  • Human Immune System Mouse
Disciplines
  • Medicine

Abstract

Abstract 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.

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