Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core

摘要: Most therapeutic agents are excluded from entering the central nervous system by blood–brain barrier (BBB). Receptor mediated transcytosis (RMT) is a common mechanism used proteins, including transferrin (Tf), to traverse BBB. Here, we prepared Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between Tf and nanoparticle core facilitate RMT across These designed bind receptors (TfRs) high avidity on blood side of BBB, but separate their multidentate Tf–TfR interactions upon acidification during process allow release into brain. targeted show increased ability cross in vitro model BBB and, most important, enter brain parenchyma mice greater amounts vivo after systemic administration compared similar high-avidity containing noncleavable Tf. In addition, investigated this design high-affinity antibodies (Abs) TfR. With Abs, addition provided no improvement uptake for Ab-containing nanoparticles, overall was decreased all Tf-containing ones. results consistent recent reports anti-TfR Abs trafficking lysosome within endothelium. contrast, high-avidity, avoid major endothelium retention shedding surface transcytosis.