Capture of stealth nanoparticles by the body's defences.
This article highlights and discusses our experience in the design, handling, and biological evaluation of long-circulating nanoparticles based on polyoxypropylene/polyoxyethylene copolymer nonionic surfactants. A frequently observed but ignored phenomenon following intravenous injection of such polymer-modified long-circulating colloidal systems is their eventual recognition and clearance by macrophages of the reticuloendothelial system. The pharmacokinetics as well as the tissue distribution of such so-called 'stealth" nanoparticles are also altered after repeated intravenous injection in a time-dependent manner. An understanding of immunological and pathological factors that control the pharmacokinetic and biological behavior of long-circulating particles after single or repeated administration is therefore crucial for the design of a system with an optimal diagnostic and/or therapeutic performance. Therefore, we have also examined and discussed the concept of macrophage recognition of a 'stealth-like nature" and factors that initiate this cascade. A critical discussion of the future of this interesting area of nano-biotechnology/engineering is also provided.
Moghimi
S M
SM
Molecular Targeting and Polymer Toxicology Group, School of Pharmacy and Biomolecular Sciences, University of Brighton, UK.
Hunter
A C
AC
D000818:Animals; D003165:Complement System Proteins / Q000276:immunology; D016503:Drug Delivery Systems; D006801:Humans; D008658:Inactivation, Metabolic; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D036103:Nanotechnology; D010316:Particle Size; D010587:Phagocytosis; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000627:therapeutic use
D011108:Polymers; D013501:Surface-Active Agents; D003165:Complement System Proteins