Accessing neuroinflammation sites: Monocyte/neutrophil-mediated drug delivery for cerebral ischemia

Hou, Jia; Yang, Xu; Li, Shiyi; Zhou, Cheng; Wang, Yuhua; Zhao, Jing; Zhang, Chun; Li, Yongji; Luo, Man; Ren, Hongwei; Liang, Jianming; Wang, Jue; Wang, Jianxin

doi:10.1126/sciadv.aau8301

Cited by 87 publications

(56 citation statements)

References 42 publications

(48 reference statements)

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“…Recently, new assessments have been applied in clinical studies to improve the outcomes of ischemic stroke. Hou et al reported the results of a new trial that showed that using monocytes and neutrophils, which were developed as carriers for cRGD [cyclo (Arg-Gly-Asp-D-Tyr-Lys)] liposomemediated drug delivery, may alleviate ischemic stroke outcomes (177). Targeting monocyte that protects neuronal cell death through nanotechnology could be a novel therapeutic strategy for ischemic stroke.…”

Section: Applied Nanotechnologiesmentioning

confidence: 99%

Monocyte Transmodulation: The Next Novel Therapeutic Approach in Overcoming Ischemic Stroke?

et al. 2020

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The immune response following neuroinflammation is a vital element of ischemic stroke pathophysiology. After the onset of ischemic stroke, a specialized vasculature system that effectively protects central nervous system tissues from the invasion of blood cells and other macromolecules is broken down within minutes, thereby triggering the inflammation cascade, including the infiltration of peripheral blood leukocytes. In this series of processes, blood-derived monocytes have a significant effect on the outcome of ischemic stroke through neuroinflammatory responses. As neuroinflammation is a necessary and pivotal component of the reparative process after ischemic stroke, understanding the role of infiltrating monocytes in the modulation of inflammatory responses may offer a great opportunity to explore new therapies for ischemic stroke. In this review, we discuss and highlight the function and involvement of monocytes in the brain after ischemic injury, as well as their impact on tissue damage and repair.

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Section: Applied Nanotechnologiesmentioning

confidence: 99%

Monocyte Transmodulation: The Next Novel Therapeutic Approach in Overcoming Ischemic Stroke?

et al. 2020

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“…Many acute and chronic inflammatory disorders in the brain involve inflammation of both the parenchyma and the vasculatures. Lastly, we sum up present BBB leakages of current studies in the condition of stroke [ 179 ], cerebral ischemia [ 180 ], sepsis [ 181 , 182 ], Malaria [ 183 , 184 ], intracellular parasite [ 185 ], SARS-CoV-2 [ 177 , 178 ], MS [ 186 ], systemic lupus erythematosus (SLE) [ 187 ], and even AD [ 188 ] and EAE [ 89 ]. Other viral infections and parasite invasion would increase the risk [ 189 , 190 , 191 ].…”

Section: Main Textmentioning

confidence: 99%

A Destruction Model of the Vascular and Lymphatic Systems in the Emergence of Psychiatric Symptoms

Segawa

Blumenthal

Yamawaki

et al. 2021

Biology

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The lymphatic system is important for antigen presentation and immune surveillance. The lymphatic system in the brain was originally introduced by Giovanni Mascagni in 1787, while the rediscovery of it by Jonathan Kipnis and Kari Kustaa Alitalo now opens the door for a new interpretation of neurological diseases and therapeutic applications. The glymphatic system for the exchanges of cerebrospinal fluid (CSF) and interstitial fluid (ISF) is associated with the blood-brain barrier (BBB), which is involved in the maintenance of immune privilege and homeostasis in the brain. Recent notions from studies of postmortem brains and clinical studies of neurodegenerative diseases, infection, and cerebral hemorrhage, implied that the breakdown of those barrier systems and infiltration of activated immune cells disrupt the function of both neurons and glia in the parenchyma (e.g., modulation of neurophysiological properties and maturation of myelination), which causes the abnormality in the functional connectivity of the entire brain network. Due to the vulnerability, such dysfunction may occur in developing brains as well as in senile or neurodegenerative diseases and may raise the risk of emergence of psychosis symptoms. Here, we introduce this hypothesis with a series of studies and cellular mechanisms.

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“…[ 8 ] Another study designed nanocarriers to attach to neutrophils and monocytes in circulation that subsequently delivered the cargo to ischemic brain tissue. [ 14 ] This demonstrates that neutrophils can be used as carrier cells for drug delivery. [ 15 ] Due to the involvement of inflammation and neutrophils in many diseases, loading neutrophils with drugs or drug‐loaded nanocarriers ex vivo and reinjecting these hybrids into the patient has the potential of becoming a vital tool to deliver drugs locally to remote inflammatory sites despite systemic administration to dampen uncontrolled inflammation.…”

Section: Figurementioning

confidence: 99%

Neutrophils Enable Local and Non‐Invasive Liposome Delivery to Inflamed Skeletal Muscle and Ischemic Heart

et al. 2020

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hampered by poor bioavailability and biostability, [3] undesirable off-target effects, [4] and obstacles presented by biological barriers, [5] thus motivating the development of drug delivery systems for efficient and localized delivery to affected tissue. Nanoparticle-based drug delivery systems for the treatment of inflammation are a powerful tool to target anti-inflammatory drugs to inflamed tissues. However, efficient local delivery remains challenging. Main hurdles include sequestration of nanoparticles by phagocytic cells and biological barriers such as the endothelium hindering infiltration and accumulation in the inflamed tissue. [6,7] Employing immune cells for active transport of drugs and drug-loaded nanocarriers to a target site is a promising recent approach. [8-10] Neutrophils are one of the most abundant, and also one of the first leukocytes to reach inflammatory tissue. [11,12] Upon activation, neutrophils can form neutrophil extracellular traps (NETs) within a few hours, a defined release mechanism that enables neutrophils to serve as a delivery system for drugs or loaded nanocarriers at early stages of inflammation. [13] These properties of neutrophils have recently been leveraged to deliver paclitaxel-loaded liposomes to suppress postoperative glioma recurrence. [8] Another study designed nanocarriers to attach to neutrophils and monocytes in circulation that subsequently Uncontrolled inflammation is a major pathological factor underlying a range of diseases including autoimmune conditions, cardiovascular disease, and cancer. Improving localized delivery of immunosuppressive drugs to inflamed tissue in a non-invasive manner offers significant promise to reduce severe side effects caused by systemic administration. Here, a neutrophil-mediated delivery system able to transport drug-loaded nanocarriers to inflamed tissue by exploiting the inherent ability of neutrophils to migrate to inflammatory tissue is reported. This hybrid system (neutrophils loaded with liposomes ex vivo) efficiently migrates in vitro following an inflammatory chemokine gradient. Furthermore, the triggered release of loaded liposomes and reuptake by target macrophages is studied. The migratory behavior of liposome-loaded neutrophils is confirmed in vivo by demonstrating the delivery of drugloaded liposomes to an inflamed skeletal muscle in mice. A single low-dose injection of the hybrid system locally reduces inflammatory cytokine levels. Biodistribution of liposome-loaded neutrophils in a human-disease-relevant myocardial ischemia reperfusion injury mouse model after i.v. injection confirms the ability of injected neutrophils to carry loaded liposomes to inflammation sites. This strategy shows the potential of nanocarrier-loaded neutrophils as a universal platform to deliver anti-inflammatory drugs to promote tissue regeneration in inflammatory diseases.

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Accessing neuroinflammation sites: Monocyte/neutrophil-mediated drug delivery for cerebral ischemia

Cited by 87 publications

References 42 publications

Monocyte Transmodulation: The Next Novel Therapeutic Approach in Overcoming Ischemic Stroke?

Monocyte Transmodulation: The Next Novel Therapeutic Approach in Overcoming Ischemic Stroke?

A Destruction Model of the Vascular and Lymphatic Systems in the Emergence of Psychiatric Symptoms

Neutrophils Enable Local and Non‐Invasive Liposome Delivery to Inflamed Skeletal Muscle and Ischemic Heart

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