Phosphorus Dendrimers Co-deliver Fibronectin and Edaravone for Combined Ischemic Stroke Treatment via Cooperative Modulation of Microglia/Neurons and Vascular Regeneration
© 2024 Wiley‐VCH GmbH..
The development of new multi-target combination treatment strategies to tackle ischemic stroke (IS) remains to be challenging. Herein, a proof-of-concept demonstration of an advanced nanomedicine formulation composed of macrophage membrane (MM)-camouflaged phosphorous dendrimer (termed as AK137)/fibronectin (FN) nanocomplexes (NCs) loaded with antioxidant edaravone (EDV) to modulate both microglia and neurons for effective IS therapy is showcased. The created MMAK137-FN/EDV (M@A-F/E) NCs with a mean size of 260 nm possess good colloidal stability, sustained EDV release kinetics, and desired cytocompatibility. By virtue of MM decoration, the M@A-F/E NCs can cross blood-brain barrier, act on microglia to exert the anti-inflammatory (AK137 and FN) and antioxidative (FN and EDV) effects in vitro for oxidative stress alleviation, microglia M2 polarization, and reduction of pro-inflammatory cytokine secretion, and act on neuron cells to be anti-apoptotic. In a transient middle cerebral artery occlusion rat model, the developed M@A-F/E NCs can exert enhanced antioxidant/anti-inflammatory/anti-apoptotic therapeutic effects to comprehensively regulate the brain microenvironment and promote vascular regeneration to collaboratively restore the blood flow after ischemia-reperfusion. The designed MM-coated NCs composed of all-active ingredients of phosphorous dendrimers, FN, and EDV that can fully regulate the brain inflammatory microenvironment may expand their application scope in other neurodegenerative diseases.
| Media Type: |
Electronic Article |
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| Year of Publication: |
2024 |
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| Publication: |
2024 |
| Contained In: |
To Main Record - year:2024 |
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| Contained In: |
Advanced healthcare materials - (2024) vom: 05. Aug., Seite e2401462 |
| Language: |
English |
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| Contributors: |
Ma, Jie [Author] |
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| Links: |
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| Keywords: |
Fibronectin |
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| Notes: |
Date Revised 05.08.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1002/adhm.202401462 |
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| funding: |
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| Supporting institution / Project title: |
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| PPN (Catalogue-ID): |
NLM37588730X |
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| 520 | |a The development of new multi-target combination treatment strategies to tackle ischemic stroke (IS) remains to be challenging. Herein, a proof-of-concept demonstration of an advanced nanomedicine formulation composed of macrophage membrane (MM)-camouflaged phosphorous dendrimer (termed as AK137)/fibronectin (FN) nanocomplexes (NCs) loaded with antioxidant edaravone (EDV) to modulate both microglia and neurons for effective IS therapy is showcased. The created MMAK137-FN/EDV (M@A-F/E) NCs with a mean size of 260 nm possess good colloidal stability, sustained EDV release kinetics, and desired cytocompatibility. By virtue of MM decoration, the M@A-F/E NCs can cross blood-brain barrier, act on microglia to exert the anti-inflammatory (AK137 and FN) and antioxidative (FN and EDV) effects in vitro for oxidative stress alleviation, microglia M2 polarization, and reduction of pro-inflammatory cytokine secretion, and act on neuron cells to be anti-apoptotic. In a transient middle cerebral artery occlusion rat model, the developed M@A-F/E NCs can exert enhanced antioxidant/anti-inflammatory/anti-apoptotic therapeutic effects to comprehensively regulate the brain microenvironment and promote vascular regeneration to collaboratively restore the blood flow after ischemia-reperfusion. The designed MM-coated NCs composed of all-active ingredients of phosphorous dendrimers, FN, and EDV that can fully regulate the brain inflammatory microenvironment may expand their application scope in other neurodegenerative diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a fibronectin | |
| 650 | 4 | |a ischemic stroke | |
| 650 | 4 | |a microglia polarizations | |
| 650 | 4 | |a phosphorus dendrimers | |
| 650 | 4 | |a revascularization | |
| 700 | 1 | |a Zhan, Mengsi |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Huxiao |e verfasserin |4 aut | |
| 700 | 1 | |a He, Liangyu |e verfasserin |4 aut | |
| 700 | 1 | |a Zou, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Tianyu |e verfasserin |4 aut | |
| 700 | 1 | |a Karpus, Andrii |e verfasserin |4 aut | |
| 700 | 1 | |a Majoral, Jean-Pierre |e verfasserin |4 aut | |
| 700 | 1 | |a Mignani, Serge |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Mingwu |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Xiangyang |e verfasserin |4 aut | |
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