A stepwise-targeting strategy for the treatment of cerebral ischemic stroke
Abstract Background Effective amelioration of neuronal damages in the case of cerebral ischemic stroke (CIS) is essential for the protection of brain tissues and their functional recovery. However, most drugs can not penetrate the blood–brain barrier (BBB), resulting in the poor therapeutic outcomes...
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2021
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oai:doaj.org-article:6d58200ddcf845078dc9f8bf31675c062021-11-21T12:29:35ZA stepwise-targeting strategy for the treatment of cerebral ischemic stroke10.1186/s12951-021-01118-61477-3155https://doaj.org/article/6d58200ddcf845078dc9f8bf31675c062021-11-01T00:00:00Zhttps://doi.org/10.1186/s12951-021-01118-6https://doaj.org/toc/1477-3155Abstract Background Effective amelioration of neuronal damages in the case of cerebral ischemic stroke (CIS) is essential for the protection of brain tissues and their functional recovery. However, most drugs can not penetrate the blood–brain barrier (BBB), resulting in the poor therapeutic outcomes. Results In this study, the derivatization and dual targeted delivery technologies were used to actively transport antioxidant melatonin (MLT) into the mitochondria of oxidative stress-damaged cells in brain tissues. A mitochondrial targeting molecule triphenylphosphine (TPP) was conjugated to melatonin (TPP-MLT) to increase the distribution of melatonin in intracellular mitochondria with the push of mitochondrial transmembrane potential. Then, TPP-MLT was encapsulated in dual targeted micelles mediated by TGN peptide (TGNYKALHPHNG) with high affinity for BBB and SHp peptide (CLEVSRKNG) for the glutamate receptor of oxidative stress-damaged neural cells.TGN/SHp/TPP-MLT micelles could effectively scavenge the overproduced ROS to protect neuronal cells from oxidative stress injury during CIS occurrence, as reflected by the improved infarct volume and neurological deficit in CIS model animals. Conclusions These promising results showed this stepwise-targeting drug-loaded micelles potentially represent a significant advancement in the precise treatment of CIS. Graphical AbstractJingbo HuXueying TanDongwei WangYixuan LiHongze LiangJiejun PengFengyan LiQuan ZhouPeiwu GengShuanghu WangYue YuJin LiuBMCarticleCerebral ischemic strokeStepwise-targeting deliveryOxidative stressMelatoninMicellesBiotechnologyTP248.13-248.65Medical technologyR855-855.5ENJournal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-17 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Cerebral ischemic stroke Stepwise-targeting delivery Oxidative stress Melatonin Micelles Biotechnology TP248.13-248.65 Medical technology R855-855.5 |
| spellingShingle |
Cerebral ischemic stroke Stepwise-targeting delivery Oxidative stress Melatonin Micelles Biotechnology TP248.13-248.65 Medical technology R855-855.5 Jingbo Hu Xueying Tan Dongwei Wang Yixuan Li Hongze Liang Jiejun Peng Fengyan Li Quan Zhou Peiwu Geng Shuanghu Wang Yue Yu Jin Liu A stepwise-targeting strategy for the treatment of cerebral ischemic stroke |
| description |
Abstract Background Effective amelioration of neuronal damages in the case of cerebral ischemic stroke (CIS) is essential for the protection of brain tissues and their functional recovery. However, most drugs can not penetrate the blood–brain barrier (BBB), resulting in the poor therapeutic outcomes. Results In this study, the derivatization and dual targeted delivery technologies were used to actively transport antioxidant melatonin (MLT) into the mitochondria of oxidative stress-damaged cells in brain tissues. A mitochondrial targeting molecule triphenylphosphine (TPP) was conjugated to melatonin (TPP-MLT) to increase the distribution of melatonin in intracellular mitochondria with the push of mitochondrial transmembrane potential. Then, TPP-MLT was encapsulated in dual targeted micelles mediated by TGN peptide (TGNYKALHPHNG) with high affinity for BBB and SHp peptide (CLEVSRKNG) for the glutamate receptor of oxidative stress-damaged neural cells.TGN/SHp/TPP-MLT micelles could effectively scavenge the overproduced ROS to protect neuronal cells from oxidative stress injury during CIS occurrence, as reflected by the improved infarct volume and neurological deficit in CIS model animals. Conclusions These promising results showed this stepwise-targeting drug-loaded micelles potentially represent a significant advancement in the precise treatment of CIS. Graphical Abstract |
| format |
article |
| author |
Jingbo Hu Xueying Tan Dongwei Wang Yixuan Li Hongze Liang Jiejun Peng Fengyan Li Quan Zhou Peiwu Geng Shuanghu Wang Yue Yu Jin Liu |
| author_facet |
Jingbo Hu Xueying Tan Dongwei Wang Yixuan Li Hongze Liang Jiejun Peng Fengyan Li Quan Zhou Peiwu Geng Shuanghu Wang Yue Yu Jin Liu |
| author_sort |
Jingbo Hu |
| title |
A stepwise-targeting strategy for the treatment of cerebral ischemic stroke |
| title_short |
A stepwise-targeting strategy for the treatment of cerebral ischemic stroke |
| title_full |
A stepwise-targeting strategy for the treatment of cerebral ischemic stroke |
| title_fullStr |
A stepwise-targeting strategy for the treatment of cerebral ischemic stroke |
| title_full_unstemmed |
A stepwise-targeting strategy for the treatment of cerebral ischemic stroke |
| title_sort |
stepwise-targeting strategy for the treatment of cerebral ischemic stroke |
| publisher |
BMC |
| publishDate |
2021 |
| url |
https://doaj.org/article/6d58200ddcf845078dc9f8bf31675c06 |
| work_keys_str_mv |
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| _version_ |
1718418950015942656 |