title: Asn-Gly-Arg-modified polydopamine-coated nanoparticles for dual-targeting therapy of brain glioma in rats.
abstract: The blood-brain barrier (BBB) is the major clinical obstacle in the chemotherapeutic management of brain glioma. Here we synthesized a pH-sensitive dual-targeting doxorubicin (DOX) carrier to compromise tumor endothelial cells, enhance BBB transportation, and improve drug accumulation in glioma cells. The drug delivery system was constructed with polydopamine (PDA)-coated mesoporous silica nanoparticles (NPs, MSNs) and the PDA coating was functionalized with Asn-Gly-Arg (NGR), a ligand with specific affinity for cluster of differentiation 13 (CD13). MSN-DOX-PDA-NGR showed a higher intracellular accumulation in primary brain capillary endothelial cells (BCECs) and C6 cells and greater BBB permeability than the non-targeting NPs (MSN-DOX-PDA) did in vitro. Ex vivo and in vivo tests showed that MSN-DOX-PDA-NGR had a higher accumulation in intracranial tumorous tissue than the undecorated NPs did. Furthermore, the antiangiogenesis and antitumor efficacy of MSN-DOX-PDA-NGR were stronger than that of MSN-DOX-PDA. Therefore, these results indicate that the dual-targeting vehicles are potentially useful in brain glioma therapy.
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.|Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.|Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China.
authors.forename: Zuhuang
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Huang
authors.affiliation: Department of Orthopaedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Si
authors.initials: S
authors.lastname: Cheng
authors.affiliation: College of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, China.
authors.forename: Huzhi
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Neurosurgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D018826:CD13 Antigens / Q000378:metabolism; D002470:Cell Survival; D004195:Disease Models, Animal; D004337:Drug Carriers; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D007211:Indoles / Q000737:chemistry; D008297:Male; D018613:Microscopy, Confocal; D057054:Molecular Imaging; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D009842:Oligopeptides / Q000008:administration & dosage*; D010539:Permeability; D011108:Polymers / Q000737:chemistry; D011485:Protein Binding; D051381:Rats; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D007211:Indoles; C526428:NGR peptide; D009842:Oligopeptides; D011108:Polymers; C568283:polydopamine; D018826:CD13 Antigens
keywords: Asn-Gly-Arg; dual-targeting; gliomas; polydopamine