Efficient intracellular drug-targeting of macrophages using stealth liposomes directed to the hemoglobin scavenger receptor CD163.
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.
Department of Biomedicine, Aarhus University, Ole Worms Alle 2, Aarhus, Denmark.
Anders
A
Etzerodt
Maciej Bogdan
MB
Maniecki
Jonas Heilskov
JH
Graversen
Holger Jon
HJ
Møller
Vladimir P
VP
Torchilin
Søren Kragh
SK
Moestrup
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology / Q000378:metabolism*; D001665:Binding Sites; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D004705:Endocytosis; D005434:Flow Cytometry; D005452:Fluoresceins / Q000008:administration & dosage / Q000494:pharmacology; D057809:HEK293 Cells; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D018613:Microscopy, Confocal; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D051116:Receptors, Scavenger / Q000276:immunology / Q000378:metabolism*; D020349:Surface Plasmon Resonance; D000098902:CD163 Antigen
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D004337:Drug Carriers; D005452:Fluoresceins; D006454:Hemoglobins; D008081:Liposomes; D011956:Receptors, Cell Surface; D051116:Receptors, Scavenger; D004317:Doxorubicin; C007740:fluorexon