title: Dual targeted nanocarrier for brain ischemic stroke treatment.
abstract: Focal cerebral ischemia, known as stroke, causes serious long-term disabilities globally. Effective therapy for cerebral ischemia demands a carrier that can penetrate the blood-brain barrier (BBB) and subsequently target the ischemia area in brain. Here, we designed a novel neuroprotectant (ZL006) loaded dual targeted nanocarrier based on liposome (T7&SHp-P-LPs/ZL006) conjugated with T7 peptide (T7) and stroke homing peptide (SHp) for penetrating BBB and targeting ischemia area, respectively. Compared with non-targeting liposomes, T7&SHp-P-LPs/ZL006 could transport across BCEC cells and significantly enhance cellular uptake and reduce cells apoptosis of excitatory amino acid stimulated PC-12 cells. However, there was no significant difference in cellular uptake between SHp-modified and plain liposomes when PC-12 cells were incubated without excitatory amino acid. Besides, ex vivo fluorescent images indicated that DiR labeled T7&SHp-P-LPs could efficiently transport across BBB and mostly accumulated in ischemic region rather than normal cerebral hemisphere of MCAO rats. Furthermore, T7&SHp-P-LPs/ZL006 could enhance the ability of in vivo anti-ischemic stroke of MCAO rats. These results demonstrated that T7&SHp-P-LPs could be used as a safe and effective dual targeted nanocarrier for ischemic stroke treatment.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Zhongyuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Lv
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Baoyan
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China; Division of Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Quanyin
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, North Carolina State University, Raleigh, NC 27695, USA; Division of Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Wujin
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China. Electronic address: Qunweixu@njmu.edu.cn.
authors.forename: Qunwei
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China. Electronic address: xhl@njmu.edu.cn.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Xin
authors.affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill, North Carolina State University, Raleigh, NC 27695, USA; Division of Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D024141:Collagen Type IV / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D065546:Drug Liberation; D018698:Glutamic Acid / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008081:Liposomes; D008297:Male; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D024141:Collagen Type IV; D008081:Liposomes; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C000591612:tumstatin (74-98); D018698:Glutamic Acid; D011092:Polyethylene Glycols
keywords: Dual-targeting liposomes; Neuroprotection; Stroke; Stroke homing peptide; ZL006