COATING PARTICLES WITH A BLOCK-COPOLYMER (POLOXAMINE-908) SUPPRESSES OPSONIZATION BUT PERMITS THE ACTIVITY OF DYSOPSONINS IN THE SERUM

The surfaces of polystyrene microspheres (60 nm in diameter) and collo idal gold particles (17 nm in diameter) were coated with a polyoxyethy lene (POE)/polyoxypropylene (POP) block co-polymer; poloxamine-908. Th e polymer adsorb strongly to the microspheres via its relatively hydro phobic POP segments. This leaves the POE chains in a mobile state as t hey extend outward from the surface and thereby provide stability to t he particle suspension by suppressing aggregation. The blood clearance and biodistribution of uncoated vs. poloxamine-908-coated I-125-label led polystyrene microspheres were compared 1 h after intravenous admin istration into rats. Poloxamine coating dramatically reduced liver acc umulation of microspheres and kept them within the systemic circulatio n. These observations were further confirmed by electron microscopy, d emonstrating that Kupffer cells were loaded with uncoated latex but ha d ingested few if any of the poloxamine-908-coated particles. The inte raction of uncoated and poloxamine-coated gold particles with freshly isolated rat liver sinusoidal cells was examined by electron microscop y. The accumulation in Kupffer cells of gold particles after opsonizat ion with autologous plasma was in accordance with previous observation s where the dominant opsonizing activity had been identified as fibron ectin. In contrast, coating of gold particles with poloxamine-908 prio r to plasma opsonization prevented the adsorption of fibronectin onto their surface. Simultaneously, Kupffer cells failed to recognize polox amine-908-coated gold particles before and after opsonization. Unlike Kupffer cells, liver endothelial cells endocytosed poloxamine-908-coat ed gold particles prior to opsonization but failed to recognize them a fter the opsonization process. This was taken as an indication of the presence of dysopsonic activity in plasma. This dysopsonic activity wa s studied using polystyrene latex microspheres, where the uptake of su ch particles by phagocytes is known to be independent of opsonization. The coating of I-125-labelled polystyrene microspheres with poloxamin e-908 dramatically reduced their interaction with liver sinusoidal cel ls. This interaction was further reduced in the presence of either aut ologous plasma or serum. A heat-stable (60 degrees C for 15 min) serum component of molecular mass > 100 kDa was found to mediate this suppr essive effect. Thus, we demonstrate that organ-specific receptors, ops onin activities and plasma dysopsonins regulate the in vivo clearance of particulate materials from the circulation. Poloxamine-908 coating modulates particle clearance by effectively blocking opsonization but still allowing for dysopsonization.