pH‐Sensitive, Cerebral Vasculature‐Targeting Hydroxyethyl Starch Functionalized Nanoparticles for Improved Angiogenesis and Neurological Function Recovery in Ischemic Stroke

Yang, Hang; Luo, Yan; Hu, Hang; Yang, Shuo; Li, Yanan; Jin, Huijuan; Chen, Shengcai; He, Quanwei; Hong, Candong; Wu, Jinjie; Li, Man; Li, Zifu; Yang, Xiangliang; Su, Ying; Zhou, Yifan; Hu, Bo

doi:10.1002/adhm.202100028

Cited by 33 publications

(28 citation statements)

References 55 publications

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“…On the other hand, angiogenic factors have adverse effects on their pleiotropic property, in turn leading to increased vascular permeability and worsened brain edema, thus resulting in hemorrhagic transformation ( Adamczak and Hoehn, 2015 ). Due to these challenges, a dual-targeted nanoparticle therapeutic strategy is proposed by combining the ECM integrin ligands and angiogenic factors ( Yang H. et al, 2021 ). In the present study, sonic hedgehog signaling protein smoothed agonist (SAG) coupled to Pro-His-Ser-Arg-Asn (PHSRN) on the hydroxyethyl starch (HES) based nanocarriers platform could be specifically released in the acidic ischemic lesion to favor angiogenesis by activating smoothened (SMO) and transcription factors ( Yang H. et al, 2021 ).…”

Section: Neurorestorative and Neuroprotective Mechanism Of Biomaterialsmentioning

confidence: 99%

“…Due to these challenges, a dual-targeted nanoparticle therapeutic strategy is proposed by combining the ECM integrin ligands and angiogenic factors ( Yang H. et al, 2021 ). In the present study, sonic hedgehog signaling protein smoothed agonist (SAG) coupled to Pro-His-Ser-Arg-Asn (PHSRN) on the hydroxyethyl starch (HES) based nanocarriers platform could be specifically released in the acidic ischemic lesion to favor angiogenesis by activating smoothened (SMO) and transcription factors ( Yang H. et al, 2021 ). In another study, PHSRN, an ECM fibronectin synergistic motif, is proposed as an attractive therapeutic option for the treatment of middle cerebral artery occlusion (MCAO) rats because it triggers angiogenesis by activating VEGF secretion-related upstream pathway and sustains the complexity of survival neurons and induces neurogenesis ( Wu et al, 2018 ).…”

Section: Neurorestorative and Neuroprotective Mechanism Of Biomaterialsmentioning

confidence: 99%

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Perspective insights into hydrogels and nanomaterials for ischemic stroke

Zhang

Yang

et al. 2023

Front. Cell. Neurosci.

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Ischemic stroke (IS) is a neurological disorder prevalent worldwide with a high disability and mortality rate. In the clinic setting, tissue plasminogen activator (tPA) and thrombectomy could restore blood flow of the occlusion region and improve the outcomes of IS patients; however, these therapies are restricted by a narrow time window. Although several preclinical trials have revealed the molecular and cellular mechanisms underlying infarct lesions, the translatability of most findings is unsatisfactory, which contributes to the emergence of new biomaterials, such as hydrogels and nanomaterials, for the treatment of IS. Biomaterials function as structural scaffolds or are combined with other compounds to release therapeutic drugs. Biomaterial-mediated drug delivery approaches could optimize the therapeutic effects based on their brain-targeting property, biocompatibility, and functionality. This review summarizes the advances in biomaterials in the last several years, aiming to discuss the therapeutic potential of new biomaterials from the bench to bedside. The promising prospects of new biomaterials indicate the possibility of an organic combination between materialogy and medicine, which is a novel field under exploration.

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Section: Neurorestorative and Neuroprotective Mechanism Of Biomaterialsmentioning

confidence: 99%

Section: Neurorestorative and Neuroprotective Mechanism Of Biomaterialsmentioning

confidence: 99%

Perspective insights into hydrogels and nanomaterials for ischemic stroke

Zhang

Yang

et al. 2023

Front. Cell. Neurosci.

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“…Small published by Wiley-VCH GmbH polysaccharide-based nanoparticles were coupled with the smoothened agonist to activate the sonic hedgehog pathway. [183] The nanoparticles were further functionalized with the Pro-His-Ser-Arg-Asn peptide that binds to the integrin α5b1 present in the cerebral vasculature of the ischemic tissue, promoting angiogenesis BBB integrity, improved neurological function, and neuroplasticity.…”

Section: (27 Of 36)mentioning

confidence: 99%

Progress in Stimuli‐Responsive Biomaterials for Treating Cardiovascular and Cerebrovascular Diseases

Tapeinos

Gao

Bauleth‐Ramos

et al. 2022

Small

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the heart, leading to the two major subcategories of cerebrovascular and cardiovascular diseases (CVDs). Both cerebral and cardiovascular diseases (CCVDs) are prevalent, leading to high percentages of mortality and morbidity worldwide. [3,4] Over the years, several medical approaches have been used to treat these diseases. For example, mechanical thrombectomy and tissue plasminogen activator (tPA) administration are the standard therapies for treating ischemic stroke that can undoubtedly help numerous patients. However, limitations like the short time window for applying these therapies (≈3-6 h) and the transformation of ischemic stroke to hemorrhagic due to tPA administration constrains their use to most patients. Following the same rationale, the standard treatment for myocardial ischemia that leads to infarction uses thrombolytics like aspirin and tissue or urokinase plasminogen activator (uPA), in combination with antihypertensives to reduce blood pressure and nitroglycerine to widen the blood vessels. Nevertheless, similar side effects as in ischemic stroke inhibit their unconditioned use. Notably, most of the current commercial treatments are focused on the imminent effects of CCVDs without considering the post-ischemia side effects. In particular, blood flow restoration followed by damage mitigation in the brain or the heart is the primary goal of the current CCVDs' treatment. Although these treatments increase the patients' survival, and to a limited extent, attenuate the disease's symptoms, they are unable to properly cure the disease due to the detrimental side effects caused by vascular ischemia.Several "smart" strategies have been suggested to eliminate the restraints of the current medical treatments and improve their therapeutic outcome. [5,6] These strategies involve using biomaterials that can read the biochemical alterations in the diseased microenvironment and respond in predetermined ways. [7,8] These "smart" biomaterials or stimuli-responsive materials can alter their physicochemical properties or structure depending on various stimuli. Additionally, they can exert a therapeutic effect either by the release of an encapsulated therapeutic (e.g., tPA/uPA) [9,10] or because of an inherent property (e.g., antioxidant CeO 2 nanoparticles (NPs)). [11][12][13] It should be noted that the stimuli can be internal, like acidic pH, platelet activation, reactive oxygen species (ROS) concentration, and enzyme concentration, or external, like magnetic and electric fields, ultrasound, and light. The reason why these stimuliresponsive biomaterials are at the forefront of research lies in the complex pathophysiology of the CCVDs that renders simple Cardiovascular and cerebrovascular diseases (CCVDs) describe abnormal vascular system conditions affecting the brain and heart. Among these, ischemic heart disease and ischemic stroke are the leading causes of death worldwide, resulting in 16% and 11% of deaths globally. Although several therapeutic approaches are presented over the years, the continuously increasin...

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“…Inspired by this, an active targeting nanoparticle system was constructed by surface conjugation of a PHSRN peptide (Pro-His-Ser-Arg-Asn) which is an integrin α ν β 1 specific binding ligand. In addition, smoothened agonist, an activator of sonic hedgehog signaling, was released in response to the acidic environment for angiogenesis promotion and neurological function recovery 128 .In another example, Deng et al . conjugated RGD peptides (arginine-glycine-aspartic acid) with hyperbranched cationic polymer (DMAPA-Amyp) to prepare RGD-DMAPA-Amyp nanoparticles for HIF-1α plasmid delivery, which could target injured endothelial cells and accumulate in the ischemic cerebral tissues 129 .…”

Section: Treatment Of Ischemic Diseases Using Nanomedicinesmentioning

confidence: 99%

Targeted delivery of nanomedicines for promoting vascular regeneration in ischemic diseases

Zhuang¹,

Zhang²,

Liu³

et al. 2022

Theranostics

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Ischemic diseases, the leading cause of disability and death, are caused by the restriction or blockage of blood flow in specific tissues, including ischemic cardiac, ischemic cerebrovascular and ischemic peripheral vascular diseases. The regeneration of functional vasculature network in ischemic tissues is essential for treatment of ischemic diseases. Direct delivery of pro-angiogenesis factors, such as VEGF, has demonstrated the effectiveness in ischemic disease therapy but suffering from several obstacles, such as low delivery efficacy in disease sites and uncontrolled modulation. In this review, we summarize the molecular mechanisms of inducing vascular regeneration, providing the guidance for designing the desired nanomedicines. We also introduce the delivery of various nanomedicines to ischemic tissues by passive or active targeting manner. To achieve the efficient delivery of nanomedicines in various ischemic diseases, we highlight targeted delivery of nanomedicines and controllable modulation of disease microenvironment using nanomedicines.

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pH‐Sensitive, Cerebral Vasculature‐Targeting Hydroxyethyl Starch Functionalized Nanoparticles for Improved Angiogenesis and Neurological Function Recovery in Ischemic Stroke

Cited by 33 publications

References 55 publications

Perspective insights into hydrogels and nanomaterials for ischemic stroke

Perspective insights into hydrogels and nanomaterials for ischemic stroke

Progress in Stimuli‐Responsive Biomaterials for Treating Cardiovascular and Cerebrovascular Diseases

Targeted delivery of nanomedicines for promoting vascular regeneration in ischemic diseases

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