Nanoparticles that avoid the ReticuloEndothelialSystem with a dense PEG copolymer coating

Resumen del trabajo presentado a la 1st Spanish Conference on Biomedical Applications of Nanomaterials (SBAN), celebrada en Madrid del 7 al 8 de junio de 2018.A crucial step for in vivo applications of nanoparticles in general and magnetic carriers in particular is to avoid the retention by the Reticuloendothelial System (RES). Without this requisite, the expectable benefits from nanoparticles in in vivo medical applications (controlled targeted delivery, reduced toxicity, early diagnosis, enhanced imaging sensitivity) will be severely limited. In vitro experiments with macrophage cell cultures (Schöttler, et al. Nat. Nanotechnol. 2016, 11, 372) have shown that an adequate polyethylenglycol (PEG) coating can prevent the macrophages uptake. In this manuscript, we show this effect in vivo using multicore iron oxide nanoparticles, opening the way for efficient targeted delivery of these type of magnetic nanocarriers in the future. The dense PEG coating is realized by Michael reaction of PEG acrylate chains on poly(4-vinylpyridine) nanoparticles embedding the iron oxide cores. Two important findings come along with the low RES retention: 1) a clear MRI contrast in kidneys is obtained for the first time with iron oxide nanoparticles; 2) the nanoparticles are excreted by the urinary system. The conclusions are supported by four independent biodistribution techniques: gamma-imaging, gamma-counting, MRI (Fig 1) and TEM histology. Moreover, the manuscript describes a new procedure for a direct radiolabeling of iron oxide nanoparticles through incorporation in the crystal lattice of 111In3+ ions.Peer reviewe