A Triple-Targeted Rutin-Based Self-Assembled Delivery Vector for Treating Ischemic Stroke by Vascular Normalization and Anti-Inflammation via ACE2/Ang1-7 Signaling.

Zhao T, He F, Zhao K, Yuxia L, Li H, Liu X, Cen J, Duan S

ACS central science5 Jun 2023Cited by 39 (Europe PMC)

PMID37396868PMCIDPMC10311651DOI10.1021/acscentsci.3c00377PepBankPUB-37396868

Summary

Changes in the cerebral microenvironment caused by acute ischemic stroke-reperfusion are the main obstacle to the recovery of neurological function and an important cause of stroke recurrence after thrombolytic therapy. The intracerebral microenvironment after ischemia-reperfusion reduces the neuroplasticity of the penumbra and ultimately leads to permanent neurological damage. To overcome this challenge, we developed a triple-targeted self-assembled nanodelivery system, which combines the neuroprotective drug rutin with hyaluronic acid through esterification to form a conjugate, and then connected SS-31, a small peptide that can penetrate the blood brain barrier and target mitochondria. Brain targeting, CD44-mediated endocytosis, hyaluronidase 1-mediated degradation, and the acidic environment synergistically promoted the enrichment of nanoparticles and drug release in the injured area. Results demonstrate that rutin has a high affinity for ACE2 receptors on the cell membrane and can directly activate ACE2/Ang1-7 signaling, maintain neuroinflammation, and promote penumbra angiogenesis and normal neovascularization. Importantly, this delivery system enhanced the overall plasticity of the injured area and significantly reduced neurological damage after stroke. The relevant mechanism was expounded from the aspects of behavior, histology, and molecular cytology. All results suggest that our delivery system may be an effective and safe strategy for the treatment of acute ischemic stroke-reperfusion injury.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study1

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone1

In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Elamipretide (SS-31).

01AnimalNot a test of Elamipretide (SS-31) aloneAnimal study (in vivo)Efficacy outcome
In a stroke-reperfusion model, a rutin-hyaluronic acid-SS‑31 delivery system significantly reduced neurological damage.
In plain wordsA delivery system made of rutin, hyaluronic acid and SS‑31 reduced brain damage after stroke in the model used. SS‑31 alone was not tested.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseNeurological damage after stroke
Study
n: not reported in source
ischemic stroke-reperfusion
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
Importantly, this delivery system enhanced the overall plasticity of the injured area and significantly reduced neurological damage after stroke.
1 context sentence(design, population, supporting numbers)
Summary · context
To overcome this challenge, we developed a triple-targeted self-assembled nanodelivery system, which combines the neuroprotective drug rutin with hyaluronic acid through esterification to form a conjugate, and then connected SS-31, a small peptide that can penetrate the blood brain barrier and target mitochondria.
In this study, Elamipretide (SS-31) was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Elamipretide (SS-31).
Show in the study text Report a problemFND-3739686801

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Version history

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Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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