Efficient intracellular drug-targeting of macrophages using stealth liposomes directed to the hemoglobin scavenger receptor CD163

Anders Etzerodt, Maciej Bogdan Maniecki, Jonas Heilskov Graversen, Holger Jon Møller, Vladimir P Torchilin, Søren Kragh Moestrup

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Abstract

The hemoglobin scavenger receptor CD163 is exclusively expressed in the monocytic lineage and preferentially in tissue resident macrophages of the M2 phenotype and in macrophages in sites of inflammation and tumor growth. In the present study we have designed liposomes specifically targeting CD163 by hydrophobic linkage of CD163-binding monoclonal antibodies to polyethylene glycol-coated liposomes ('stealth liposomes'). Targeting to the endocytic CD163 protein greatly increased the uptake of liposomes in CD163 transfected cells and macrophages as visualized by confocal microscopy and flow cytometry of cells exposed to CD163 targeting liposomes loaded with calcein. Strong cytotoxic effects were seen in CD163-expressing human monocytes by using the chemotherapeutic agent doxorubicin as cargo of the liposomes. In conclusion, the use of stealth liposomes modified to recognize CD163 is a potential way to target drugs to macrophages that support inflammatory and malignant processes.
OriginalsprogEngelsk
TidsskriftJournal of Controlled Release
ISSN0168-3659
DOI
StatusUdgivet - 2012

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