Nose-to-Brain Delivery of mRNA-Loaded Lipid Nanoparticles Bypasses the Blood–Brain Barrier for Effective Brain Disease Therapy

 For when our researchers finally discover drugs to repair the brain.

Nose-to-Brain Delivery of mRNA-Loaded Lipid Nanoparticles Bypasses the Blood–Brain Barrier for Effective Brain Disease Therapy

• Xiaolu Yu
• Xiao-Meng Deng
• Yi Lin
• Hongyu Ren
• Lu Jia
• Yanan Meng
• Fan Liu
• Qiang Cheng*
• Zhao-Qian Teng*
• Tuo Wei*

Abstract

mRNA-loaded lipid nanoparticles (mRNA-LNPs) show great therapeutic potential, but their use in central nervous system (CNS) disorders is limited by poor blood–brain barrier (BBB) penetration. Intranasal (IN) administration can bypass the BBB via olfactory/trigeminal pathways, enabling direct brain targeting and rapid screening of brain-specific lipid nanoparticles (LNPs). Using a peptide-based ionizable lipid platform, we systematically evaluated how LNP surface charge affects IN brain delivery and found that positively charged mRNA-LNPs produced superior brain transfection. Iterative in vivo screening yielded an intranasal brain-targeting LNP (INBT LNP) that efficiently traverses the olfactory and trigeminal nerves, drives brain-specific mRNA expression, and minimizes off-target expression in peripheral organs. Co-delivery of mRNAs encoding brain-derived neurotrophic factor (BDNF) and interleukin-10 (IL-10) using INBT LNPs significantly reduced neuroinflammation, inhibited neuronal death, and improved cognition in a repetitive mild traumatic brain injury (rmTBI) mouse model. Overall, this work establishes a noninvasive, patient-compliant, intranasal mRNA-LNP platform for brain delivery, offering a promising therapeutic strategy for TBI and other CNS disorders.

© 2026 American Chemical Society

• Tuo Wei*

Researchers develop ‘breakthrough’ nasay[sic] spray for stroke

 Ask your competent? doctor EXACTLY what this contains and the method of action.  This said absolutely nothing useful!

So quiz your doctor on all this other nasal research! NO knowledge is grounds for termination!

•  nasal delivery (10 posts to December 2017)
• intranasal delivery (8 posts to June 2022)
• dihydroergotamine nasal powder (2 posts to May 2025)
• /,13 nasal delivery options (6 posts to April 2014)

Researchers develop ‘breakthrough’ nasay[sic] spray for stroke

A nasal spray designed to protect brain cells after stroke could offer a new prehospital emergency option, researchers say.

Researchers say the approach could help slow brain cell death and buy time for clot-removing or clot-busting treatment.

The spray has been developed by scientists at the University of Hong Kong, who describe it as the world’s first nasal spray designed to protect brain cells immediately after stroke.

Stroke is a leading cause of death and disability, with researchers citing an annual global healthcare burden of more than US$890bn.

Current stroke treatment usually begins after hospital admission and can involve clot-breaking drugs or reperfusion therapies, which aim to restore blood flow through arteries going to the brain.

The window for effective treatment is narrow, meaning more than 85 per cent of patients are unable to receive treatment quickly enough.

Researchers said many brain-targeting drugs also fail in trials because they cannot cross the blood-brain barrier.

The blood-brain barrier is the brain’s protective filter. It helps keep harmful substances out of the brain, but can also stop medicines reaching the area where they are needed.

Aviva Chow Shing-fung, from the University of Hong Kong, said: “The failure rate of drug candidates targeting the central nervous system in clinical trials exceeds 90 per cent, largely because these drugs cannot cross the blood-brain barrier, and thus fail to reach the brain to exert their therapeutic effects.”

To address this, the team developed a “Nanopowder” nasal spray containing brain-protective drugs(What are they?) in ultra-small inhalable powders.

The spray is inhaled into the nasal cavity, where it settles in the target area and separates into nanoparticles.

These tiny particles then travel through the nose-to-brain pathway, bypassing the blood-brain barrier.

Researchers said this could deliver the drug directly to the brain and provide early protection while a patient is being taken to hospital.

They reported that giving the nasal spray within 30 minutes of stroke onset reduced brain tissue death by more than 80 per cent in their tests.

They also said the spray protected neurological and body movement functions, reduced inflammation, helped prevent cell death and supported the integrity of the blood-brain barrier.

Neurological functions are abilities controlled by the brain and nervous system, such as movement, speech, memory and coordination.

Shao Zitong, a postdoctoral fellow at the University of Hong Kong, said: “After a stroke, every second matters.

“Even an additional 10 minutes of brain protection might determine whether a patient can walk or speak in the future.

“The key breakthrough of this technology lies in shifting stroke treatment from the ‘in-hospital’ setting to the ‘prehospital’ stage, enabling neuroprotection rather than merely clot dissolution or thrombectomy.”

Micro/Nanoparticles in the Nose-Brain Axis: Implications for Pathogenesis and Therapeutic Interventions

 Your competent? doctor is already aware of the nose to brain axis and diligently working on solutions for survivor recovery, right? OH NO! Knows nothing AND does nothing! You really picked the worst of the lot. And your board of directors is so incompetent they can't recognize incompetence in their hospital!

• nose-to-brain (3 posts to June 2024)

Micro/Nanoparticles in the Nose-Brain Axis: Implications for Pathogenesis and Therapeutic Interventions

 Authors:  Mou YK, Wang Y, Wang HR , Cheng YC, Shen H, Ren C Song XC 

Received 28 November 2025 

Accepted for publication 16 March 2026

Published 3 April 2026 

Volume 2026:21 585021 

DOI https://doi.org/10.2147/IJN.S585021 

Checked for plagiarism;Yes 

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Sachin Mali

Download Article [PDF] 

Ya-Kui Mou,^{1– 4,*} Quan Li,^2,5,* Yao Wang,^{1– 4,*} Xiao-Yu Song,^{1– 4} Han-Rui Wang,^{1– 4} Wan-Chen Liu,^{1– 4} Yuan-Chao Cheng,^{1– 4} Hui Shen,^{1– 4} Chao Ren,^2,6,7 Xi-Cheng Song<sup>1– 4

1</sup>Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; ²Shandong Provincial Key Laboratory of Neuroimmune Interaction and Regulation, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China; ³Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, People’s Republic of China; ⁴Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; ⁵Department of Emergency, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; ⁶Department of Neurology, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; ⁷Yantai Municipal Key Medical and Health Laboratory of Yantai Yuhuangding Hospital (Interdisciplinary Brain Science and Geriatric Health Laboratory), Qingdao University, Yantai, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Chao Ren, Department of Neurology. Yantai Yuhuangding Hospital, Qingdao University, No. 20, East Road, Zhifu District, Yantai, 264000, People’s Republic of China, Tel +86535 6691999, Fax +86535 6240341, Email renchaotg@126.com Xi-Cheng Song, Department of Otolaryngology, Head and Neck Surgery. Yantai Yuhuangding Hospital, Qingdao University, No. 20, East Road, Zhifu District, Yantai, 264000, People’s Republic of China, Tel +86535 6691999, Fax +86535 6240341, Email drxchsong@163.com

Abstract: The nose-brain axis (NBA) is a crucial bidirectional deliverypathway between the nasal cavity and the central nervous system (CNS) that influences both neurophysiology and disease progression. In addition to serving as a route for drug delivery, the NBA plays an active role in neurological disorders by mediating inflammatory responses, microbial interactions, and environmental exposure. Emerging evidence suggests that the NBA may be mechanistically relevant to CNS disorders, particularly within neurodegeneration frameworks such as the Braak and dual-hit hypotheses, which emphasize early olfactory or other peripheral involvements. This review explores how micro/nanoparticles interact with the NBA, not only as therapeutic carriers but also as factors contributing to neuroinflammation and neurodegeneration. Pathogenic micro/nanoparticles, including environmental pollutants and industrial nanoparticles, have been implicated in the exacerbation of CNS disorders by triggering oxidative stress and immune activation in both nasal and brain tissues. Conversely, therapeutic micro/nanoparticles such as biomimetic, synthetic, and cell-derived formulations represent promising strategies for modulating neuroinflammation, enhancing neuroprotection, and restoring CNS function through nasal-targeted interventions. However, substantial gaps remain in the existing understanding of the influences of nasal immune responses, microbiota, and barrier integrity on CNS health through the NBA. Addressing these challenges is critical for leveraging micro-/nanoparticles for the prevention and treatment of CNS diseases.

Low-Power-Activated Afterglow Nanoprobes With Naked-Eye Visibility for High-Contrast Imaging of Brain Inflammation

 You'll need your competent? doctor and hospital to get human testing going so they can objectively identify your brain inflammation and come up with ways to prevent it.

Do you prefer your doctor, hospital and board of director's incompetence NOT KNOWING? OR NOT DOING? Your choice; let them be incompetent or demand action!

Low-Power-Activated Afterglow Nanoprobes With Naked-Eye Visibility for High-Contrast Imaging of Brain Inflammation

Jiangnan Ouyang, Yanqiu Li, Rui Chen, Xianlong Su, Zhihong Liu

First published: 21 February 2026

 

https://doi.org/10.1002/anie.3145716Digital Object Identifier (DOI)

 

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ABSTRACT

Afterglow luminescence imaging ingeniously circumvents the need for real-time excitation, thereby substantially eliminating background interference. Nevertheless, its application in brain imaging has been hindered by low afterglow brightness under aqueous conditions. Here, we present naked-eye-visible afterglow nanoprobes excited by low-power light for high-contrast imaging of brain inflammation. By strategically integrating highly efficient donor–acceptor–donor (D–A–D) luminescent molecules into photochemical afterglow systems, we developed a series of ultrabright afterglow materials emitting in the yellow, orange, and red spectral regions. The resulting afterglow nanoparticles remain naked-eye detectable even under ultralow excitation power (0.73 mW cm−2). Their afterglow brightness is over 1300 times higher than that of commonly used afterglow nanoparticles, and they still maintain a 3-fold advantage compared to previously developed blue-emitting nanoparticles based on molecular fusion strategies. Leveraging this exceptional performance, we accomplished real-time naked-eye observation of freely moving mice. Moreover, macrophage-encapsulated nanoparticles enabled blood–brain barrier (BBB) penetration and high-contrast imaging of brain inflammation. This work introduces a new paradigm for constructing high-brightness afterglow materials and opens transformative avenues for real-time visualization of brain disorders.

Graphical Abstract

By integrating D–A–D molecules into photochemical afterglow systems, we developed nanoprobes exhibiting naked-eye-detectable afterglow under low-power excitation (0.73 mW cm−2). Their brightness is 1305 times higher than that of common afterglow nanoparticles such as MEHPPV-NPs, enabling naked-eye tracking of freely moving mice and high-contrast imaging of brain inflammation.

Conflicts of Interes

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Dual Ligand Cooperation at the Plasma Membrane Drives Transport of Engineered Small Extracellular Vesicles Across Brain Endothelial Cells

Our stroke medical 'professionals' can explain how this can be used to get new neurons moved to the right places via neurogenesis. At least if they have more than two functioning neurons to rub together.

 This snippet from the email blast is great for us:
The efficacy of these strategies has been supported by therapeutic outcomes in
preclinical models of stroke, Alzheimer’s and Parkinson’s disease… 
Dual Ligand Cooperation at the Plasma Membrane Drives Transport of Engineered Small Extracellular Vesicles Across Brain Endothelial Cells

Inês Albino†,‡, Elena Ambrosetti§,, Ana Teixeira§, Paula Sampaio⊥,, Miguel M. Lino*,†,‡, & Lino Ferreira*,†,‡ 

 † Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal. 

 ‡ IIIUC-Institute of Interdisciplinary Research, University of Coimbra, Coimbra, Portugal. 

  Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. 

 § Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. 

 ⊥ Institute for Research and Innovation in Health (I3S), University of Porto, Porto, Portugal. 

  Institute for Molecular and Cellular Biology (IBMC), University of Porto, Porto, Portugal. 

ABSTRACT The copyright holder for this preprint bioRxiv preprint doi: https://doi.org/10.64898/2026.01.21.700773 ; this version posted January 23, 2026. (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The natural delivery properties of small ABSTRACT The copyright holder for this preprint bioRxiv preprint doi: https://doi.org/10.64898/2026.01.21.700773 ; this version posted January 23, 2026. (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. The natural delivery properties of small extracellular vesicles (sEVs) can be harnessed and enhanced through engineering to create a new class of biotherapeutics, particularly for central nervous system (CNS) disorders. While evidence supports the ability of sEVs to cross biological barriers and deliver functional cargo to target cells, a limited understanding of their uptake and transport across the brain hinders their translational potential. In this study, we investigated either native and engineered sEVs, developed by us, using a novel modular engineering platform that employs a dual-targeting strategy to facilitate uptake and transport through human brain endothelial cells (BECs). By utilizing super-resolution microscopy, we provided direct insights into the mechanisms of docking, intracellular sorting, and transport of engineered sEVs. The engineered sEVs formulation demonstrated significantly enhanced uptake, intracellular trafficking across BECs, and the ability to bypass degradative pathways. In vivo, the engineered sEVs exhibited preferential accumulation in the brain choroid plexus, a structure located within the lateral and fourth ventricles, thereby effectively targeting the blood-cerebrospinal fluid (CSF) barrier. These findings highlight the potential of combining advanced targeting strategies with high-resolution imaging to study sEV interactions with the brain biological barriers and develop more effective CNS therapies. vesicles (sEVs) can be harnessed and enhanced through engineering to create a new class of biotherapeutics, particularly for central nervous system (CNS) disorders. While evidence supports the ability of sEVs to cross biological barriers and deliver functional cargo to target cells, a limited understanding of their uptake and transport across the brain hinders their translational potential. In this study, we investigated either native and engineered sEVs, developed by us, using a novel modular engineering platform that employs a dual-targeting strategy to facilitate uptake and transport through human brain endothelial cells (BECs). By utilizing super-resolution microscopy, we provided direct insights into the mechanisms of docking, intracellular sorting, and transport of engineered sEVs. The engineered sEVs formulation demonstrated significantly enhanced uptake, intracellular trafficking across BECs, and the ability to bypass degradative pathways. In vivo, the engineered sEVs exhibited preferential accumulation in the brain choroid plexus, a structure located within the lateral and fourth ventricles, thereby effectively targeting the blood-cerebrospinal fluid (CSF) barrier. These findings highlight the potential of combining advanced targeting strategies with high-resolution imaging to study sEV interactions with the brain biological barriers and develop more effective CNS therapies.

Transplanted Iron Oxide Nanoparticle-Labeled Mesenchymal Stem Cells Exhibit ex vivo Neuronal Firing Activity in Ischemic Stroke Rats

 

 Great, now can your incompetent? doctor and hospital get human testing going?

Do you prefer your doctor and hospital incompetence NOT KNOWING? OR NOT DOING?

Transplanted Iron Oxide Nanoparticle-Labeled Mesenchymal Stem Cells Exhibit ex vivo Neuronal Firing Activity in Ischemic Stroke Rats

Authors Huang DM, Lu CW , Hsiao JK 

Received 25 February 2025

Accepted for publication 15 August 2025

Published 28 August 2025 Volume 2025:20 Pages 10469—10486

DOI https://doi.org/10.2147/IJN.S518933

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. RDK

Dong-Ming Huang,¹ Chen-Wen Lu,² Jong-Kai Hsiao<sup>2,3

1</sup>Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan; ²Department of Medical Imaging, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan; ³School of Medicine, Tzu Chi University, Hualien, Taiwan

Correspondence: Jong-Kai Hsiao, Department of Medical Imaging, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 289, Jian Guo Road, Xindian District, New Taipei City, 23142, Taiwan, Tel +886-2-6628-9779-61714, Fax +886-2-86272976, Email jongkai@tzuchi.com.tw

Purpose: Mesenchymal stem cell (MSC) therapy shows promise in preclinical ischemic stroke models, yet clinical translation remains inconsistent. To address this gap, we investigated whether labeling MSCs with Ferucarbotran enables magnetic resonance imaging (MRI) tracking and enhances neural differentiation and functional integration, particularly focusing on the novel observation of spontaneous neuronal firing activity in transplanted cells.
Methods: Rat MSCs (rMSCs) were transduced with red fluorescent protein (RFP) and labeled with Ferucarbotran to generate Fer-RFP⁺ rMSCs. These were transplanted into rats subjected to middle cerebral artery occlusion. MRI tracked cell migration and localization. Behavioral recovery was evaluated via the corner test, modified neurological severity score (mNSS), and infarct volume analysis. Post-transplantation, Fer-RFP⁺ rMSCs were magnetically isolated for ex vivo electrophysiological and immunocytochemical analyses.
Results: Ferucarbotran labeling did not impair rMSC viability and enhanced in vitro proliferation. MRI effectively visualized Fer-RFP⁺ rMSC migration to ischemic regions. Rats receiving Fer-RFP⁺ rMSCs showed significantly improved functional recovery and reduced infarct volumes compared to controls. Remarkably, ex vivo isolated Fer-RFP⁺ rMSCs exhibited spontaneous neuronal firing on multi-electrode array recordings and expressed the neuronal marker NeuN.
Conclusion: Ferucarbotran-labeled MSCs not only serve as MRI-visible tracers but also exhibit neuronal electrophysiological properties post-transplantation in an ischemic stroke model. The emergence of spontaneous neuronal firing in ex vivo transplanted MSCs suggests functional neuronal differentiation, potentially underpinning the observed therapeutic effects. These findings offer new mechanistic insights into MSC-mediated stroke recovery and may enhance the translational relevance of MSC-based therapies.

Keywords: mesenchymal stem cells, iron oxide nanoparticles, ischemic stroke, magnetic resonance imaging, neural differentiation, neuronal firing activity

Recent Advancements in Lipid Nanoparticles-Based Phytoactives Delivery Systems for Neurodegenerative Diseases

 Will you competent? doctor and hospital ENSURE RESEARCH IS CREATED that tests whether this could be used to prevent Parkinsons and Alzheimers post stroke? Oh no, your doctor and hospital ARE DOING NOTHING!

The reason you need dementia prevention: 

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.

3. A 20% chance in this research.   July 2013. 

Parkinson’s Disease May Have Link to Stroke March 2017 

The latest here:

Recent Advancements in Lipid Nanoparticles-Based Phytoactives Delivery Systems for Neurodegenerative Diseases

Authors Dirir AM, Ali A, Hachem M

Received  29 April 2025Accepted for publication 8 July 2025  Published 25 August 2025 Volume 2025:20 Pages 10279—10300 DOI https://doi.org/10.2147/IJN.S537566

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Dong Wang

Amina M Dirir,¹ Abdelmoneim Ali,² Mayssa Hachem<sup>1,3

1</sup>Department of Chemistry, College of Engineering and Physical Sciences, Khalifa University of Science and Technology, Abu Dhabi, 127788, United Arab Emirates; ²Department of Food Science, College of Agriculture and Veterinary Medicine, United Arab Emirates University (UAEU), Al Ain, 15551, United Arab Emirates; ³Food Security and Technology Center, Khalifa University of Science and Technology, Abu Dhabi, 127788, United Arab Emirates

Correspondence: Mayssa Hachem, Email mayssa.hachem@ku.ac.ae

Abstract: Neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases, pose a significant and continuous burden on the healthcare system, urging the search for innovative therapeutical approaches targeting the central nervous system. Nowadays, no definitive treatment can effectively modulate the neuronal degeneration associated with such diseases. The current line of therapies is primarily symptomatic and suffers several drawbacks. Among these, phytochemicals are emerging for their potential in the management of neurodegenerative disorders. Indeed, plants produce secondary metabolites that provide defensive functions against abiotic and biotic stresses. These metabolites can target the neurons and represent a promising therapeutic intervention for neurological disorders. However, the polar nature of phytochemicals and their large size hinder their passage through the blood-brain barrier, a selective barrier separating blood and the brain. Emerging studies have shown that the therapeutic efficiency of phytochemicals has been enhanced following their encapsulation with engineered nanocarriers such as lipid nanoparticles. Recent research indicates that delivering phytochemicals through lipid nanoparticles improves their physiological stability, promotes their passage across the blood-brain barrier, and enhances their accumulation in brain tissue—resulting in more effective neuroprotective effects than their free, unencapsulated form. Hence, the aim of the present review is to highlight the application of lipid nanoparticles as carriers for phytoactives with neuroprotective properties, discuss the current challenges associated with such nanocarriers, and provide insights into potential future research work.

A Wideband Multimodal Flexible Sensor Integrating Vertical Graphene and Sea Urchin-Like Nanoparticles for Post-Stroke Rehabilitation

 Do you really think your competent? doctor has enough functioning brain cells to get this into your stroke hospital?

Do you prefer your doctor and hospital incompetence NOT KNOWING? OR NOT DOING?

A Wideband Multimodal Flexible Sensor Integrating Vertical Graphene and Sea Urchin-Like Nanoparticles for Post-Stroke Rehabilitation

Geng Zhong Qingzhou Liu, Yunjun Huang, Haoyang Geng, Tailin Xu, First published: 21 August 2025 https://doi.org/10.1002/adma.202508206 

Stroke is a leading cause of long-term disability worldwide, with post-stroke aphasia significantly impairing communication and social interaction. Traditional rehabilitation devices are often bulky, expensive, and impractical for daily use, particularly in speech recovery, where accessible and effective solutions remain limited. To address this challenge, this study introduces a portable and wearable sensor system for stroke-induced aphasia rehabilitation. The proposed sensor integrates a flexible, ultrasensitive, and durable dual-sensor system comprising an Ag-MnO2-based sea-urchin-like nanoparticle pressure sensor to detect high-frequency vocal vibrations and a vertical graphene/polydimethylsiloxane (VGr/PDMS) strain sensor to capture low-frequency muscular movements. The sensors, integrated into a flexible circuit, employ an encoder-cycle-consistent generative adversarial networks (CycleGAN) model that recognizes users' intent and recovers voice, significantly reducing dependency on large-scale labelled datasets. Experimental results demonstrate accurate intent recognition with accuracies for certain commands exceeding 95%. The reconstructed speech exhibits improved naturalness based on objective and perceptual evaluations, highlighting potential clinical utility in enhancing daily communication and interaction for stroke survivors.

Graphical Abstract

This work presents a speech reconstruction framework based on a dual-sensor system that collects wideband signals from vocal vibrations and throat muscle movements. An encoder-cycle-consistent generative adversarial networks (CycleGAN) model maps the signals to speech without requiring a large-scale paired training dataset. The system achieves over 95% intent recognition accuracy and generates natural-sounding speech with a mean opinion score of 2.9.

Conflict of Interest

The authors declare no conflict of interest.

Emerging Targeted Delivery Strategies of Nanosystems for Ischemic Stroke Treatment

 Nothing occurred with this a decade ago, nothing will occur with this. 

To prove total incompetence in stroke, nothing was done with this:

Making neurons from stem cells: Molecular mechanisms and spider silk substrates November 2013

THERE IS NO LEADERSHIP IN STROKE!

Nothing will happen!

Emerging Targeted Delivery Strategies of Nanosystems for Ischemic Stroke Treatment

Authors Ren JX, Ma HY, Yin WJ, Li YK, Lei SY, Liu JC, Yang Y, Guo ZN

Received 25 January 2025

Accepted for publication 11 May 2025

Published 24 June 2025 Volume 2025:20 Pages 8143—8171

DOI https://doi.org/10.2147/IJN.S519328

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 6

Editor who approved publication: Dr Xing Zhang

Download Article [PDF] 

Jia-Xin Ren,^1,* Hong-Yin Ma,^1,* Wen-Jing Yin,¹ Yi-Kai Li,² Shuang-Yin Lei,¹ Jia-Cheng Liu,¹ Yi Yang,¹ Zhen-Ni Guo<sup>1,3

1</sup>Stroke Center, Department of Neurology, the First Hospital of Jilin University, Chang Chun, People’s Republic of China; ²The First Norman Bethune Clinical Medical College, Jilin University, Chang Chun, People’s Republic of China; ³Neuroscience Research Center, Department of Neurology, the First Hospital of Jilin University, Chang Chun, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yi Yang, Department of Neurology, the First Hospital of Jilin University, Xinmin Street 1#, Changchun, 130021, People’s Republic of China, Tel +86-13756661217, Fax +86-431-88782378, Email yang_yi@jlu.edu.cn Zhen-Ni Guo, Department of Neurology, the First Hospital of Jilin University, Xinmin Street 1#, Changchun, 130021, People’s Republic of China, Tel +86-18186872986, Fax +86-431-88782378, Email zhen1ni2@jlu.edu.cn

Abstract: Ischemic stroke is a leading cause of death and severe disability worldwide. Current treatments mainly focus on reperfusion and neuroprotection. However, due to limitations like a narrow treatment window, single therapeutic targets, and side effects, drug therapy effectiveness is often unsatisfactory. Additionally, the blood-brain barrier (BBB) and the pathophysiological changes following ischemia pose challenges in stroke treatment. Recent developments in nanomaterials have enabled the design of multifunctional drug delivery nanosystems to advance stroke therapeutic approaches. These novel treatments significantly overcome the shortcomings of current therapies and improve efficacy. This review comprehensively summarizes innovative strategies for drug delivery nanosystems, which include crossing the BBB to target the ischemic region and controllable release in a responsive manner. Smart nanosystems, due to the modification of specific ligands and/or cell membranes, can cross the BBB to target the ischemic region for precise treatment, achieving controlled release and specific accumulation of drugs through intelligent molecular switching. Combining different strategies to build drug delivery nanosystems allows for positioning and targeted accumulation of drugs in the ischemic region, thereby extending the therapeutic time window and synergistically improving the neuroprotective effects. Such combinations provide a powerful strategy for developing novel ischemic stroke treatments and establishing targeting delivery nanosystems. Furthermore, the review summarizes the challenges encountered by multifunctional drug delivery nanosystems including clinical translation, drug loading capacity, and safety concerns, and potential solutions.

Keywords: ischemic stroke, nanosystems, targeting therapy, blood-brain barrier, controllable release

Graphical Abstract: