Acid‐Responsive Transferrin Dissociation and GLUT Mediated Exocytosis for Increased Blood–Brain Barrier Transcytosis and Programmed Glioma Targeting Delivery

• DOI: 10.1002/adfm.201802227
• Publication Date: 2018-05-28T07:07:17Z
• Authors: Shaobo Ruan; Lin Qin; Wei Xiao; Chuan Hu; Yang Zhou; Ranran Wang; Xing Sun; Wenqi Yu; Qin He; Huile Gao
• Keywords: Transcytosis; Parenchyma; Transferrin receptor

Abstract Receptor mediated transcytosis (RMT) is a common mechanism used for nanotherapeutics to traverse the blood–brain barrier (BBB). However, of ligand modified nanoparticles via RMT likely be trapped within brain capillary endothelial cells due high binding affinity with receptors, which greatly reduces amount across BBB. Here, P‐aminophenyl‐α‐D‐mannopyranoside (MAN) decorated doxorubicin‐loaded dendrigraft poly‐l‐lysine acid‐cleavable transferrin (Tf) coating outside (DD‐MCT) proposed. The DD‐MCT engineered specifically recognize Tf receptor (TfR) on luminal side BBB endothelium. Then undergoes an acid‐responsive cleavage Tf, leading separation MAN‐decorated DGL‐DOX (DD‐M) from Tf–TfR complex in endo/lysosomes. detached DD‐M more prone escape endo/lysosomes and can further exocytosed into parenchyma mediation glucose transporter located abluminal membrane. Moreover, target glioma cells. Significantly, enters greater amounts, resulting enhanced accumulation at site thus improved antiglioma therapeutic outcome. This strategy pioneers new path reducing trapping endothelium but increasing their parenchyma.