Targeting of MPEG-protected polyamino acid carrier to human E-selectin in vitro.
Targeted diagnostic agents are expected to have a significant impact in molecular imaging of cell-surface associated markers of proliferation, inflammation and angiogenesis. In this communication, we describe a new class of targeted polyamino acid-based protected graft copolymers (PGC) of poly-(L-lysine) and methyl poly-(ethylene glycol) (PGC) covalently conjugated with a monoclonal antibody fragment, F(ab')(2). We utilized targeted PGC conjugates as carriers of near-infrared indocyanine fluorophores (Cy5.5) for optical imaging of endothelial cell populations expressing IL-1 beta inducible proinflammatory marker E-selectin. We compared two conjugation chemistries, involving either introduction of sulfhydryl group to F(ab')(2), or via direct attachment of the antibody fragment directly to the chemically activated PGC. Both PGC-based targeted agents demonstrated high binding specificity (20-30 fold over non-specific uptake) and were utilized for imaging E-selectin expression on human endothelial cells activated with IL-1 beta.
Kang
H W
HW
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
Weissleder
R
R
Bogdanov
A
A
D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism*; D002232:Carbocyanines / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D019040:E-Selectin / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*
D000596:Amino Acids; C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D004337:Drug Carriers; D019040:E-Selectin; D007140:Immunoglobulin Fab Fragments; D007375:Interleukin-1; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol