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Proposed mechanism for the delivery of the drug and antibody combination to brain metastases using acid-cleavable targeting ligands. At extracellular pH 7.4, Tf ligands and Herceptin remain bound to the diols on the nanoparticle surface. After endocytosis, rapid acidification of the endosome to pH 5.5 triggers their dissociation from the nanoparticle core, allowing free diffusion into the brain once transcytosis is complete.
