title: Hydrazinonicotinamide prolongs quantum dot circulation and reduces reticuloendothelial system clearance by suppressing opsonization and phagocyte engulfment.
abstract: In this study, we investigated the effects of hydrazinonicotinamide (HYNIC)-a bifunctional crosslinker widely used to (99m)Tc radiolabel protein and nanoparticles for imaging studies-on quantum dot opsonization, macrophage engulfment and in vivo kinetics. In streptavidin-coated quantum dots (SA-QDots), conjugation with HYNIC increased the net negative charge without affecting the zeta potential. Confocal microscopy and fluorescence-activated cell sorting showed HYNIC attachment to suppress SA-QDot engulfment by macrophages. Furthermore, HYNIC conjugation suppressed surface opsonization by serum protein including IgG. When intravenously injected into mice, HYNIC conjugation significantly prolonged the circulation of SA-QDots and reduced their hepatosplenic uptake. Diminished reticuloendothelial system clearance of SA-QDots and aminoPEG-QDots by HYNIC conjugation was also demonstrated by in vivo and ex vivo optical imaging. The effects of HYNIC on the opsonization, phagocytosis and in vivo kinetics of quantum dots were reversed by removal of the hydrazine component from HYNIC. Thus, surface functionalization with HYNIC can improve the in vivo kinetics of quantum dots by reducing phagocytosis via suppression of surface opsonization.
authors.affiliation: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kyung-Ho
authors.initials: KH
authors.lastname: Jung
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Park
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Paik
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Lee
authors.forename: Yearn Seong
authors.initials: YS
authors.lastname: Choe
authors.forename: Kyung-Han
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000737:chemistry; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D012157:Mononuclear Phagocyte System / Q000502:physiology*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry; D009895:Opsonin Proteins / Q000378:metabolism*; D010587:Phagocytosis / Q000502:physiology*; D045663:Quantum Dots
chemical_list: D003432:Cross-Linking Reagents; D009895:Opsonin Proteins; C530514:hydrazinonictinamide; D009536:Niacinamide