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Immuno
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Nano-Pharmacology: Nanotechnology Based Therapeutics for Targeting Neuroinflammation
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Nano-Pharmacology: Nanotechnology Based Therapeutics for Targeting Neuroinflammation

A special issue of Immuno (ISSN 2673-5601). This special issue belongs to the section "Neuroimmunology".

Deadline for manuscript submissions: closed (28 February 2026) | Viewed by 11677

Special Issue Editor

Dr. Supriya Mahajan

E-Mail Website
Guest Editor
Department of Medicine, Division of Allergy, Immunology & Rheumatology, State University of New York at Buffalo, New York, NY, USA
Interests: apoptosis and cell death; bioinformatics; endocrinology; gene expression; gene therapy; genomics and proteomics; immunology; molecular and cellular biology; molecular basis of disease; neurobiology; RNA; viral pathogenesis

Special Issue Information

Dear Colleagues,

Neuroimmunology is reshaping the understanding of the central nervous system (CNS). Neuroinflammation is a complex process that involves the activation of microglia, astrocytes, and other immune cells in the brain. Significant advances have been made in developing nano-formulations to target microglia, astrocytes, and other immune cells in the brain, thereby reducing neuroinflammation and protecting neurons from injury. The chapters in this Special Issue will cover translational studies in the field that highlight the role of microglia, astrocytes, and the blood–brain barrier (BBB) in orchestrating neuroimmune dynamics. Our Special Issue will focus on various nano-pharmacology aspects that involve using nanotechnology tools, such as novel drug carriers, which facilitate the selection of efficacious combinations of pharmaceuticals. Ultimately, their goal is centered around increasing therapeutic efficacy and reducing drug toxicity in the context of CNS disorders, such as drug addiction, Alzheimer’s disease, glioblastomas, traumatic brain injuries, and co-morbidities associated with HIV.

Dr. Supriya Mahajan
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Immuno is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • nano-pharmacology
  • nanotherapeutics
  • neuroinflammation
  • neuroimmunology
  • blood–brain barrier (BBB)
  • neurological diseases
  • central nervous system (CNS)
  • microglia/astrocytes/pericytes/brain microvascular endothelial cells
  • neural cells
  • dopaminergic neurons
  • computational neuroscience
  • neuroplasticity

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Published Papers (5 papers)

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Research

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24 pages, 2324 KB  
Article
Size-Based Targeting of Anti-Inflammatory Nanoparticles for Drug Delivery to Blast-Injured BBB for TBI Treatment
by Rebecca R. Schmitt, Sonali Garg, Tracey A. Ignatowski, Kathiravan Kaliyappan, Vijaya Prakash Krishnan Muthaiah, Paras N. Prasad and Supriya D. Mahajan
Immuno 2026, 6(2), 29; https://doi.org/10.3390/immuno6020029 - 20 Apr 2026
Viewed by 390
Abstract
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with blast TBI (bTBI) particularly affecting military personnel and individuals exposed to explosive environments, yet there are no available curative treatments to date. While adrenergic receptor antagonists have shown promise [...] Read more.
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide, with blast TBI (bTBI) particularly affecting military personnel and individuals exposed to explosive environments, yet there are no available curative treatments to date. While adrenergic receptor antagonists have shown promise in reducing neuroinflammation and improving TBI mortality rates, systemic administration of these drugs can have deleterious effects including bradycardia and hypotension. Here, we introduce a polymeric nanoparticle system for the delivery of adrenergic receptor antagonists, which allows for size-based targeting of the injured blood–brain barrier (BBB). These nanoparticles consist of chitosan-coated polylactic co-glycolic acid encapsulating the β-adrenergic receptor antagonist propranolol and/or the α-adrenergic receptor antagonist phenoxybenzamine. Particles designed with a 200 nm hydrodynamic diameter showed a 20–24% increase in permeability on an in vitro contact co-culture BBB model exposed to a 23 or 35 PSI acoustic blast when compared to uninjured controls, whereas 100 nm particles show no difference, suggesting blast injury induces BBB damage that enables the accumulation of larger particles. Treatment of blast-injured human brain microvascular cells with our nanoformulation reduced extracellular inflammatory cytokine levels and reduced the expression of pro-inflammatory markers in microglia. Moreover, these particles mitigated the upregulation of extracellular TNFα induced by free phenoxybenzamine in injured and uninjured microglia, suggesting nanoparticle drug encapsulation can reduce adverse drug reactions in the brain. Together, these findings provide proof-of-concept for size-based targeting and the potential anti-inflammatory effects of CS-PLGA nanoparticles containing adrenergic receptor antagonists for treatment of TBI and bTBI. Full article
(This article belongs to the Special Issue Nano-Pharmacology: Nanotechnology Based Therapeutics for Targeting Neuroinflammation)
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Review

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28 pages, 1118 KB  
Review
Neurotoxic Effects of Metal and Metal Oxide Nanoparticles and the Protective Role of Natural Bioactive Compounds
by Muhammed Zahid Sahin
Immuno 2026, 6(2), 20; https://doi.org/10.3390/immuno6020020 - 27 Mar 2026
Viewed by 830
Abstract
Nanomaterials (NMs) are increasingly utilized in drug delivery, diagnostic imaging, and therapeutic applications. However, their widespread use raises concerns regarding potential neurotoxicity, particularly for metal and metal oxide nanoparticles. Accumulating evidence indicates that these nanoparticles induce neurotoxicity through interconnected mechanisms, including excessive reactive [...] Read more.
Nanomaterials (NMs) are increasingly utilized in drug delivery, diagnostic imaging, and therapeutic applications. However, their widespread use raises concerns regarding potential neurotoxicity, particularly for metal and metal oxide nanoparticles. Accumulating evidence indicates that these nanoparticles induce neurotoxicity through interconnected mechanisms, including excessive reactive oxygen species generation, activation of neuroinflammatory pathways, mitochondrial dysfunction, and disruption of blood–brain barrier integrity. These molecular events collectively lead to synaptic impairment, neuronal apoptosis, and progressive cognitive and behavioral deficits, with toxicity severity influenced by dose, exposure duration, and age. Given that in vitro models often fail to capture complex systemic interactions such as nanoparticle biodistribution, blood–brain barrier dynamics, and neuroimmune responses, this review places particular emphasis on in vivo studies to provide a more physiologically relevant understanding of nanoparticle-induced neurotoxicity. Importantly, a growing body of in vivo evidence demonstrates that natural bioactive compounds can mitigate these effects by targeting key pathogenic pathways, including oxidative stress, inflammation, and mitochondrial dysfunction, while preserving neuronal integrity. These findings highlight the therapeutic potential of natural bioactives as protective agents against nanoparticle-induced neurotoxicity and as candidates for broader neuroprotective strategies. This review summarizes the mechanistic basis of metal and metal oxide nanoparticle neurotoxicity and critically evaluates the protective role of natural bioactive compounds, with a focus on evidence derived from animal models. Full article
(This article belongs to the Special Issue Nano-Pharmacology: Nanotechnology Based Therapeutics for Targeting Neuroinflammation)
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42 pages, 2233 KB  
Review
Nanobiotechnology-Based Strategies for Targeting Neuroinflammation and Neural Tissue Engineering
by Tejas Yuvaraj Suryawanshi, Neha Redkar, Akanksha Sharma, Jyotsna Mishra, Sumit Saxena and Shobha Shukla
Immuno 2026, 6(1), 18; https://doi.org/10.3390/immuno6010018 - 13 Mar 2026
Viewed by 1006
Abstract
Neuroinflammation is a central hallmark of numerous neurological disorders, including Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, and spinal cord damage. Its persistent and dysregulated nature not only accelerates neuronal loss but also impedes endogenous repair, posing a major challenge for effective therapeutic [...] Read more.
Neuroinflammation is a central hallmark of numerous neurological disorders, including Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, and spinal cord damage. Its persistent and dysregulated nature not only accelerates neuronal loss but also impedes endogenous repair, posing a major challenge for effective therapeutic intervention. Recent advances in nanobiotechnology have opened transformative opportunities to modulate neuroinflammation with unprecedented precision while simultaneously supporting neural regeneration. This review highlights emerging nanomaterial-based strategies including lipid-based, polymeric, inorganic nanoparticles designed to traverse the blood–brain barrier (BBB), deliver anti-inflammatory agents, modulate immune cell behavior, and attenuate glial activation. Extending beyond nanoparticle-based delivery systems, recent advances also emphasize the integration of nanomaterials into biomimetic architectures to provide structural and functional cues for neural repair. We further summarize how these functional nanostructured scaffolds, such as extracellular matrix (ECM) mimetic, nanofibrous and conductive hydrogels, are being leveraged in neural tissue engineering to direct stem cell fate, promote axonal outgrowth, and rebuild damaged neuroarchitectures. Moreover, pharmacokinetics, biodistribution, safety, clinical trials, regulatory considerations and limitations of nanotherapeutics in neurodegenerative diseases are discussed. By outlining the current progress, mechanistic insights, and translational challenges, this review underscores the potential of nanobiotechnology-enabled therapeutics to revolutionize the treatment of neuroinflammatory conditions and advance next-generation neural repair technologies. Full article
(This article belongs to the Special Issue Nano-Pharmacology: Nanotechnology Based Therapeutics for Targeting Neuroinflammation)
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28 pages, 4884 KB  
Review
Extracellular Vesicles in Neuroinflammation: Insights into Pathogenesis, Biomarker Potential, and Therapeutic Strategies
by Uma Maheswari Deshetty, Seema Singh, Frida L. Martínez-Cuevas, Stuti Jain, Shilpa Buch and Palsamy Periyasamy
Immuno 2026, 6(1), 12; https://doi.org/10.3390/immuno6010012 - 3 Feb 2026
Cited by 1 | Viewed by 1464
Abstract
Extracellular vesicles (EVs) constitute a heterogeneous group of membrane-derived particles generated through distinct biogenesis pathways, each regulated by precise molecular mechanisms. They carry a diverse array of cargo that reflects the physiological or pathological state of their parent cells. Their classification continues to [...] Read more.
Extracellular vesicles (EVs) constitute a heterogeneous group of membrane-derived particles generated through distinct biogenesis pathways, each regulated by precise molecular mechanisms. They carry a diverse array of cargo that reflects the physiological or pathological state of their parent cells. Their classification continues to evolve, as advances in isolation and characterization techniques have revealed novel vesicle subpopulations beyond the traditional categories of microvesicles, and apoptotic bodies, further highlighting the complexity of the EV landscape. Within the central nervous system (CNS), neurons, microglia, astrocytes, oligodendrocytes, and endothelial cells actively release EVs that contribute to intercellular communication. Growing evidence demonstrates that these vesicles play critical roles in neuroinflammation and neurodegeneration by transporting bioactive molecules that influence disease pathways. Their ability to cross the blood–brain barrier allows CNS-derived EVs to be detected in peripheral fluids, making them promising candidates for noninvasive biomarkers. Moreover, EVs are increasingly being explored as therapeutic tools due to their stability, biocompatibility, and capacity to deliver targeted molecular cargo. In this review, we provide a comprehensive overview of EV biogenesis and release mechanisms in CNS cell types, discuss their emerging functions in neuroinflammatory and neurodegenerative disorders, and summarize current advances in EV-based diagnostics and therapeutic approaches, including ongoing clinical trials. Full article
(This article belongs to the Special Issue Nano-Pharmacology: Nanotechnology Based Therapeutics for Targeting Neuroinflammation)
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28 pages, 992 KB  
Review
Efficacy of Intravenous Immunoglobulins and Other Immunotherapies in Neurological Disorders and Immunological Mechanisms Involved
by Angel Justiz-Vaillant, Sachin Soodeen, Odalis Asin-Milan, Julio Morales-Esquivel and Rodolfo Arozarena-Fundora
Immuno 2025, 5(2), 18; https://doi.org/10.3390/immuno5020018 - 26 May 2025
Cited by 3 | Viewed by 7389
Abstract
This review aims to explore the role of immunotherapeutic strategies—primarily intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and selected immunomodulatory agents—in the treatment of neurological and psychiatric disorders with suspected or confirmed autoimmune mechanisms. A central focus is placed on understanding the immunopathology of [...] Read more.
This review aims to explore the role of immunotherapeutic strategies—primarily intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and selected immunomodulatory agents—in the treatment of neurological and psychiatric disorders with suspected or confirmed autoimmune mechanisms. A central focus is placed on understanding the immunopathology of these conditions through the identification and characterization of disease-associated autoantibodies. Disorders such as autoimmune encephalitis, myasthenia gravis, limbic epilepsy, neuropsychiatric systemic lupus erythematosus (NPSLE), and certain forms of schizophrenia have shown clinical responses to immunotherapy, suggesting an underlying autoimmune basis in a subset of patients. The review also highlights the diagnostic relevance of detecting autoantibodies targeting neuronal receptors, such as NMDA and AMPA receptors, or neuromuscular junction components, as biomarkers that guide therapeutic decisions. Furthermore, we synthesize findings from published randomized controlled trials (RCTs) that have validated the efficacy of IVIG and PLEX in specific diseases, such as Guillain–Barré syndrome, and myasthenia gravis. Emerging clinical evidence supports expanding these treatments to other conditions where autoimmunity is implicated. By integrating immunological insights with clinical trial data, this review offers a comprehensive perspective on how immunotherapies may be tailored to target autoimmune contributors to neuropsychiatric disease. Full article
(This article belongs to the Special Issue Nano-Pharmacology: Nanotechnology Based Therapeutics for Targeting Neuroinflammation)
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