Real-time evidence of surface modification at polystyrene lattices by poloxamine 908 in the presence of serum: in vivo conversion of macrophage-prone nanoparticles to stealth entities by poloxamine 908.
Intravenously injected polystyrene nanoparticles, which are prone to rapid sequestration by professional phagocytes, are converted to stealth entities by prior bolus intravenous injection of poloxamine 908. This behaviour is not due to alteration in macrophage phagocytic activity. Laser Doppler anemometry and surface plasmon resonance were used to unravel the mechanisms fundamental to generation of such stealth entities in vivo by poloxamine 908. Electrophoretic mobility of poloxamine pre-coated monodisperse polystyrene nanoparticles in serum, which behave as stealth entities in vivo, was similar to that of uncoated nanoparticles incubated in poloxamine pre-treated serum. This observation supported the notion that poloxamine in serum can modify the surface of nanoparticles with similar topography to that of stealth poloxamine pre-coated particles, i.e. with polyoxyethylene chains projected from the surface. Surface plasmon resonance optical phenomenon was used for real-time monitoring of protein-poloxamine interactions and adsorption at the polystyrene interface. It was found that poloxamine can not only adsorb to a serum-modified surface but in addition poloxamine in serum can form macromolecular complexes with high affinity for adsorption to a polystyrene lattice. A role for serum albumin in surface modification of nanoparticles by poloxamine 908 is also identified. Hence, our biophysical observations correlate precisely with the in vivo longevity of uncoated polystyrene nanoparticles in poloxamine pre-treated rats. This rational and sensitive biophysical approach has unravelled the probable mechanism fundamental to generation of stealth entities in vivo and therefore has application in the design and nano-engineering of stealth colloidal carriers for optimal biological performance.
Moghimi
S M
SM
Molecular Targeting and Polymer Toxicology Group, School of Pharmacy and Biomolecular Sciences, University of Brighton, BN2 4GJ, Brighton, UK. s.m.moghimi@brighton.ac.uk <s.m.moghimi@brighton.ac.uk>
Pavey
K D
KD
Hunter
A C
AC
D000818:Animals; D001798:Blood Proteins / Q000737:chemistry*; D002417:Cattle; D004337:Drug Carriers; D005029:Ethylenediamines / Q000737:chemistry*; D007074:Immunoglobulin G / Q000737:chemistry; D007700:Kinetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D012709:Serum Albumin / Q000737:chemistry*; D020349:Surface Plasmon Resonance; D013499:Surface Properties
D001798:Blood Proteins; D004337:Drug Carriers; D005029:Ethylenediamines; D007074:Immunoglobulin G; D012709:Serum Albumin; C012571:tetronic 701; D011092:Polyethylene Glycols