THE ROLE OF SERUM COMPLEMENT ON THE ORGAN DISTRIBUTION OF INTRAVENOUSLY ADMINISTERED POLY (METHYL-METHACRYLATE) NANOPARTICLES - EFFECTS OF PRE-COATING WITH PLASMA AND WITH SERUM COMPLEMENT

Purpose. The organ distribution of radiolabeled poly (methyl methacryl ate) (PMMA) nanoparticles coated with plasma proteins and serum comple ment in rats was studied in order to determine the effect of serum com plement on the particle phagocytosis by the organs of the reticulo-end othelial system (RES). Methods. PMMA-nanoparticles were coated overnig ht with plasma proteins or serum complement, and injected into Wistar rats. The body distribution of nanoparticles was measured by means of scintillation counting of organ samples. In addition, proteins adsorbe d to the particle surface were inactivated by heat treatment prior to injection, and the particles's distribution was measured as described above. Results. Whereas uncoated nanoparticles (control group) were ma inly taken up by the Kupffer cells in the liver, incubation of the par ticles in plasma for 12 h followed by heat inactivation reduced the pa rticle concentrations in the liver to merely 22% after 30 min. After 1 20 min, liver concentrations were still lower than the control group, and almost 30% of the administered dose of the heat-inactivated partic le group was present in non-RES organs and tissues. Particles with non -inactivated complement were accumulated in the lung at concentrations of 29% after 30 min, which increased to 71% after 120 min, whereas th ose coated with inactivated complement reached lung concentrations abo ve 70% already after 30 min. Conclusions. Particles coated with plasma components are able to avoid uptake by the RES, especially after heat inactivation of the plasma components adsorbed. Adsorption and heat i nactivation of complement proteins alone, however, does not have the s ame result as coating with plasma proteins followed by heat inactivati on. Therefore, it is concluded that plasma components other than compl ement proteins take part in the process of RES activation and phagocyt osis of injected nanoparticles.