title: Delivery of a peptide-drug conjugate targeting the blood brain barrier improved the efficacy of paclitaxel against glioma.
abstract: The challenge of effectively delivering therapeutic agents to the brain has created an entire field of active research devoted to overcoming the blood brain barrier (BBB) and efficiently delivering drugs to the brain. Angiopep-2 can trigger transcytosis and traverse the BBB by recognizing low-density lipoprotein related protein-1 (LRP-1) expressed on the brain capillary endothelial cells. Here, we designed a novel strategy for the delivery of drugs to the brain. The novel drug delivery system was a combination of a receptor-targeting ligand, such as low-density lipoprotein related protein 1, and a cell-penetrating peptide (CPP). It was hypothesized that this conjugate will enhance the delivery of associated therapeutic cargo across the BBB and increase the permeability of a solid tumor. Our findings indicate that the combination of these two agents in a delivery vehicle significantly improved translocation of small molecules (paclitaxel) into the brain compared to the vehicle treatment, which contained only receptor-targeting ligand. The application of this strategy could potentially expand the horizons for the treatment of central nervous system disorders.
authors.affiliation: Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Tianjin Institute of Pharmaceutical Research, Tianjin, China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Zheng
authors.affiliation: School of Pharmacy, Tianjin Medical University, Tianjin, China.|Department of Oncology, University of Oxford, Oxford, UK.
authors.forename: Min
authors.initials: M
authors.lastname: Gong
authors.affiliation: Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000737:chemistry; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D023041:Xenograft Model Antitumor Assays
chemical_list: C531860:Angiopep-2; D057846:Cell-Penetrating Peptides; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010455:Peptides; D017239:Paclitaxel
keywords: blood brain barrier; brain glioma; cell penetrating peptide; low-density lipoprotein related protein-1; paclitaxel