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: Yue Zhao, Yan Jiang, Wei Lv, Zhongyuan Wang, Lingyan Lv, Baoyan Wang, Xin Liu, Yang Liu, Quanyin Hu, Wujin Sun, Qunwei Xu, Hongliang Xin, Zhen Gu
• Journal: Journal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 233 Pg. 64-71 (07 10 2016) ISSN: 1873-4995 [Electronic] Netherlands
• PMID: 27142584 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Collagen Type IV
• Liposomes
• Neuroprotective Agents
• Peptide Fragments
• tumstatin (74-98)
• Glutamic Acid
• Polyethylene Glycols

Topics

• Animals
• Apoptosis (drug effects)
• Brain (drug effects, metabolism, pathology)
• Cell Line
• Cell Line, Tumor
• Collagen Type IV (administration & dosage, chemistry, therapeutic use)
• Drug Liberation
• Glutamic Acid (pharmacology)
• Infarction, Middle Cerebral Artery (drug therapy, metabolism, pathology)
• Liposomes
• Male
• Mice, Inbred ICR
• Nanoparticles (administration & dosage, chemistry, therapeutic use)
• Neurons (drug effects)
• Neuroprotective Agents (administration & dosage, chemistry, therapeutic use)
• Peptide Fragments (administration & dosage, chemistry, therapeutic use)
• Polyethylene Glycols (chemistry)
• Rats, Sprague-Dawley
• Stroke (drug therapy, metabolism, pathology)