Selective targeting of nanocarriers to neutrophils and monocytes.
We previously identified and characterized cell-type selective binding peptides from random peptide phage display libraries. Here, we used one of these peptides (GGP) to target liposomal nanocarriers to leukocyte subsets. To profile the binding selectivity of GGP-coated liposomes to human blood cells, we performed flow cytometric analysis with whole anti-coagulated blood. It is shown that when liposomal nanocarriers present these peptides on their surface, they facilitated cell-type specific targeting of liposomes to neutrophils and monocytes in contrast to nontargeted liposomes. Our data suggest that engineering the appropriate number of targeting peptide ligands on the nanocarrier surface is a factor in cell-binding selectivity, as is dose. Increasing the peptide density on the surface of the liposomes from 250 to 500 molecules resulted in more binding to neutrophils and monocytes. Fluorescence confocal microscopy corroborated the flow cytometry data revealing that liposomes coated with targeting GGP peptides decorated the surface of targeting cells and facilitate cell uptake of payload as evidenced by nuclear localization of tracer. These data suggest that small peptides identified by phage display techniques can be used to target nanocarriers that potentially carry therapeutic or imaging agents to leukocyte subsets. This ability has important implications for diseases where neutrophils and monocytes play a major role such as arthritis, inflammatory bowel disease, chronic obstructive pulmonary disease, and glomerulonephritis.
Karathanasis
Efstathios
E
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Geigerman
Cissy M
CM
Parkos
Charles A
CA
Chan
Leslie
L
Bellamkonda
Ravi V
RV
Jaye
David L
DL
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D002478:Cells, Cultured; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D009000:Monocytes / Q000378:metabolism*; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D009504:Neutrophils / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin