Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core
Copyright policy )Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core
Significance Treatment for many neurological diseases is hindered by the inability of therapeutic agents to cross the blood–brain barrier (BBB). Here, we show a method for increasing the ability of high-avidity, transferrin (Tf)-containing nanoparticles to enter the brain through transcytosis. Tf was attached to nanoparticles through an acid-cleavable linkage that facilities release of nanoparticles from Tf that are bound to Tf receptors (TfR) during transcytosis, promoting entry of the nanoparticles into the brain. This method is an improvement over previous high-affinity, TfR-targeted therapeutics that were restricted by BBB endothelium and mostly excluded from entering the brain. Increased brain accumulation of nanoparticles via this methodology should allow for greater delivery of encapsulated therapeutic agents at lower systemic doses.
- California Institute of Technology United States
Antibody Affinity, transcytosis, 610, Metal Nanoparticles, Antibodies, Cell Line, Cell Line, Tumor, Receptors, Transferrin, therapeutic delivery, Animals, Humans, Endothelium, Mice, Inbred BALB C, Transferrin, Brain, blood–brain barrier, in vivo, systemic administration, Blood-Brain Barrier, Female, Gold, Transcytosis, Acids, Protein Binding
Antibody Affinity, transcytosis, 610, Metal Nanoparticles, Antibodies, Cell Line, Cell Line, Tumor, Receptors, Transferrin, therapeutic delivery, Animals, Humans, Endothelium, Mice, Inbred BALB C, Transferrin, Brain, blood–brain barrier, in vivo, systemic administration, Blood-Brain Barrier, Female, Gold, Transcytosis, Acids, Protein Binding
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