Nanotechnology approaches to drug delivery for the treatment of ischemic stroke.

Ischemic stroke is a major global public health concern that lacks effective treatment options. A significant challenge lies in delivering therapeutic agents to the brain due to the restrictive nature of the blood-brain barrier (BBB). The BBB's selectivity hampers the delivery of therapeutically relevant quantities of agents to the brain, resulting in a lack of FDA-approved pharmacotherapies for stroke. In this article, we review therapeutic agents that have been evaluated in clinical trials or are currently undergoing clinical trials. Subsequently, we survey strategies for synthesizing and engineering nanoparticles (NPs) for drug delivery to the ischemic brain. We then provide insights into the potential clinical translation of nanomedicine, offering a perspective on its transformative role in advancing stroke treatment strategies. In summary, existing literature suggests that drug delivery represents a major barrier for clinical translation of stroke pharmacotherapies. While nanotechnology has shown significant promise in addressing this challenge, further advancements aimed at improving delivery efficiency and simplifying formulations are necessary for successful clinical translation.

Red light-induced localized release of carbon monoxide for alleviating postoperative cognitive dysfunction.

Inflammation within the central nervous system (CNS), which may be triggered by surgical trauma, has been implicated as a significant factor contributing to postoperative cognitive dysfunction (POCD). The relationship between mitigating inflammation at peripheral surgical sites and its potential to attenuate the CNS inflammatory response, thereby easing POCD symptoms, remains uncertain. Notably, carbon monoxide (CO), a gasotransmitter, exhibits pronounced anti-inflammatory effects. Herein, we have developed carbon monoxide-releasing micelles (CORMs), a nanoparticle that safely and locally liberates CO upon exposure to 650 nm light irradiation. In a POCD mouse model, treatment with CORMs activated by light (CORMs + hv) markedly reduced the concentrations of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-alpha (TNF-α) in both the peripheral blood and the hippocampus, alongside a decrease in ionized calcium-binding adapter molecule 1 in the hippocampal CA1 region. Furthermore, CORMs + hv treatment diminished Evans blue extravasation, augmented the expression of tight junction proteins zonula occludens-1 and occludin, enhanced neurocognitive functions, and fostered fracture healing. Bioinformatics analysis and experimental validation has identified Htr1b and Trhr as potential key regulators in the neuroactive ligand-receptor interaction signaling pathway implicated in POCD. This work offers new perspectives on the mechanisms driving POCD and avenues for therapeutic intervention.

Highly BBB-permeable nanomedicine reverses neuroapoptosis and neuroinflammation to treat Alzheimer's disease.

The prevalence of Alzheimer's disease (AD) is increasing globally due to population aging. However, effective clinical treatment strategies for AD still remain elusive. The mechanisms underlying AD onset and the interplay between its pathological factors have so far been unclear. Evidence indicates that AD progression is ultimately driven by neuronal loss, which in turn is caused by neuroapoptosis and neuroinflammation. Therefore, the inhibition of neuroapoptosis and neuroinflammation could be a useful anti-AD strategy. Nonetheless, the delivery of active drug agents into the brain parenchyma is hindered by the blood-brain barrier (BBB). To address this challenge, we fabricated a black phosphorus nanosheet (BP)-based methylene blue (MB) delivery system (BP-MB) for AD therapy. After confirming the successful preparation of BP-MB, we proved that its BBB-crossing ability was enhanced under near-infrared light irradiation. In vitro pharmacodynamics analysis revealed that BP and MB could synergistically scavenge excessive reactive oxygen species (ROS) in okadaic acid (OA)-treated PC12 cells and lipopolysaccharide (LPS)-treated BV2 cells, thus efficiently reversing neuroapoptosis and neuroinflammation. To study in vivo pharmacodynamics, we established a mouse model of AD mice, and behavioral tests confirmed that BP-MB treatment could successfully improve cognitive function in these animals. Notably, the results of pathological evaluation were consistent with those of the in vitro assays. The findings demonstrated that BP-MB could scavenge excessive ROS and inhibit Tau hyperphosphorylation, thereby alleviating downstream neuroapoptosis and regulating the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Overall, this study highlights the therapeutic potential of a smart nanomedicine with the capability of reversing neuroapoptosis and neuroinflammation for AD treatment.

Engineered 3D human neurovascular model of Alzheimer's disease to study vascular dysfunction.

The blood-brain barrier (BBB) serves as a selective filter that prevents harmful substances from entering the healthy brain. Dysfunction of this barrier is implicated in several neurological diseases. In the context of Alzheimer's disease (AD), BBB breakdown plays a significant role in both the initiation and progression of the disease. This study introduces a three-dimensional (3D) self-assembled in vitro model of the human neurovascular unit to recapitulate some of the complex interactions between the BBB and AD pathologies. It incorporates primary human brain endothelial cells, pericytes and astrocytes, and stem cell-derived neurons and astrocytes harboring Familial AD (FAD) mutations. Over an extended co-culture period, the model demonstrates increased BBB permeability, dysregulation of key endothelial and pericyte markers, and morphological alterations mirroring AD pathologies. The model enables visualization of amyloid-beta (Aß) accumulation in both neuronal and vascular compartments. This model may serve as a versatile tool for neuroscience research and drug development to provide insights into the dynamic relationship between vascular dysfunction and AD pathogenesis.

GLP-1 programs the neurovascular landscape.

Readily available nutrient-rich foods exploit our inherent drive to overconsume, creating an environment of overnutrition. This transformative setting has led to persistent health issues, such as obesity and metabolic syndrome. The development of glucagon-like peptide-1 receptor (GLP-1R) agonists reveals our ability to pharmacologically manage weight and address metabolic conditions. Obesity is directly linked to chronic low-grade inflammation, connecting our metabolic environment to neurodegenerative diseases. GLP-1R agonism in curbing obesity, achieved by impacting appetite and addressing associated metabolic defects, is revealing additional benefits extending beyond weight loss. Whether GLP-1R agonism directly impacts brain health or does so indirectly through improved metabolic health remains to be elucidated. In exploring the intricate connection between obesity and neurological conditions, recent literature suggests that GLP-1R agonism may have the capacity to shape the neurovascular landscape. Thus, GLP-1R agonism emerges as a promising strategy for addressing the complex interplay between metabolic health and cognitive well-being.

Neuroinflammation and blood-brain barrier breakdown in acute, clinical intracerebral hemorrhage.

Neuroinflammation is a promising therapeutic target in intracerebral hemorrhage (ICH), characterized in the brain by microglial activation and blood-brain barrier (BBB) breakdown. In this study, 36 acute, spontaneous, supratentorial ICH patients underwent dynamic contrast-enhanced MRI to measure BBB permeability (Ktrans) 1-3 days post-onset and 16 returned for [11C](R)-PK11195 PET to quantify microglial activation (BPND), 2-7 days post-onset. We first tested if these markers were increased and co-localized in the perihematomal brain and found that perihematomal Ktrans and BPND were increased vs. the contralateral brain, but regions of high Ktrans and BPND only overlapped by a mean of 4.9%. We then tested for associations of perihematomal Ktrans and BPND with clinical characteristics (age, ICH volume & location, blood pressure), other markers of inflammation (edema, IL-6, and CRP), and long-term functional outcome (90-day mRS). Lower perihematomal BPND was associated with increasing age. Lobar hemorrhage was associated with greater Ktrans than deep, but Ktrans and BPND were not associated with ICH volume, or other inflammatory markers. While perihematomal Ktrans and BPNDwere not associated with outcome, contralateral Ktrans was significantly associated with greater 90-day mRS. Exploratory analyses demonstrated that blood pressure variability over 72 h was also associated with contralateral Ktrans.

Salidroside improves blood-brain barrier integrity and cognitive function in hypobaric hypoxia mice by inhibiting microglia activation through GSK3ß.

Salidroside, an active component found in Rhodiola rosea L., has emerged as a potential therapeutic agent for the prevention and treatment of hypoxic brain injury, while the precise target and mechanism of salidroside were remain unclear. The study utilized techniques such as network pharmacology, transcriptome sequencing to investigate the mechanism and target of salidroside in regulating blood-brain barrier (BBB) function to protect hypoxic brain injury in vivo. Utilized macromolecular docking and molecular biology techniques to explore the molecular mechanism of salidroside in alleviating brain injury induced by hypoxia in BV2 cell model. The results show that salidroside alleviated the learning and memory dysfunction and pathological injury in mice exposed to hypobaric hypoxia, reduced brain water content and attenuate the inflammatory response and oxidative stress, effectively reversed S100ß in serum and promoted the repair of BBB. GSK3ß is an important therapeutic target of salidroside in the treatment of hypoxic cognitive impairment, and salidroside can specifically bind GSK3ß in the ATP binding pocket, inducing the phosphorylation of GSK3ß, targeting downstream Nrf-2 to regulate microglia activity, promoting the accumulation of ß-catenin, thereby inhibiting microglial activation, improving the BBB integrity injury and achieving a neuroprotective effect. This study demonstrates that salidroside can inhibit the activation of microglia by inducing GSK3ß phosphorylation, achieve neuroprotective effects and alleviate learning and memory dysfunction in hypobaric hypoxia mice. This study provides a theoretical basis for the development of salidroside and the clinical application of Rhodiola rosea L.

Omega-3 Polyunsaturated Fatty Acids and Blood-Brain Barrier Integrity in Major Depressive Disorder: Restoring Balance for Neuroinflammation and Neuroprotection.

Major depressive disorder (MDD), affecting over 264 million individuals globally, is associated with immune system dysregulation and chronic neuroinflammation, potentially linked to neurodegenerative processes. This review examines blood-brain barrier (BBB) dysfunction in MDD, focusing on key regulators like matrix metalloproteinase 9 (MMP9), aquaporin-4 (AQP4), and ATP-binding cassette subfamily B member 1 (ABCB1). We explore potential mechanisms by which compromised BBB integrity in MDD may contribute to neuroinflammation and discuss the therapeutic potential of omega-3 polyunsaturated fatty acids (n-3 PUFAs). n-3 PUFAs have demonstrated anti-inflammatory and neuroprotective effects, and potential ability to modulate MMP9, AQP4, and ABCB1, thereby restoring BBB integrity in MDD. This review aims to elucidate these potential mechanisms and evaluate the evidence for n-3 PUFAs as a strategy to mitigate BBB dysfunction and neuroinflammation in MDD.

Utilizing Multifaceted Approaches to Target Drug Delivery in the Brain: From Nanoparticles to Biological Therapies.

The blood-brain barrier (BBB) poses an important obstacle to treating neurological disorders because it limits the entry of therapeutic agents into the central nervous system (CNS). Surmounting this barrier is crucial for delivering drugs effectively and targeting precise areas of the brain affected by conditions like Parkinson's disease, Alzheimer's disease, and brain tumors. This review examines the diverse strategies employed to enhance brain targeting, including nanotechnology, viral vectors, and biological therapies. Nanoparticles, liposomes, and dendrimers offer promising approaches for encapsulating drugs and facilitating their transport across the BBB. Viral vectors, such as adeno-associated viruses, demonstrate high transfection efficiency for gene therapy applications in CNS diseases. Biological therapies, including stem cell transplantation and neuromodulation techniques, can potentially restore normal cellular function and treat genetic disorders. Challenges such as BBB permeability, safety concerns, and regulatory considerations are discussed, along with future perspectives on precision medicine, noninvasive delivery methods, and biomarker discovery. By addressing these challenges and embracing innovative approaches, the field of brain drug targeting aims to transfer the way that neurological illness is treated and improve patient outcomes.

Barriers of the CNS transfer rate dynamics in patients with vascular cognitive impairment and dementia.

Background: Advances in in vivo MRI techniques enable cerebral barrier transfer rates (K trans ) measurement in patients with vascular cognitive impairment and dementia (VCID). However, a consensus has not been reached on the dynamic contribution and importance of cerebral barrier abnormalities to the differential diagnosis of dementia subtypes. Our goal was to investigate the dynamics of blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) K trans in patients with VCID longitudinally and determine the effect of aging. Methods: We studied subjects at two time points over two years; they were 65.5 years of age (SD = 15.94, M/F = 24/14) at the first visit. We studied 38 patients, 18 of whom had two visits. We calculated the BBB and BCSFB K trans with dynamic contrast-enhanced T1 MR, and we used 1H-MR spectroscopy to measure N-acetylaspartate (NAA) levels in the white matter as a marker of injury. In addition, we measured CSF levels of active-matrix metalloproteinase-3 (MMP3) as an inflammatory biomarker to aid in patient clustering. Results: Longitudinal BBB measurements revealed variable dynamic behavior: after two years, the BBB K trans increased in 55% of patients and decreased in the remaining 45% unpredictably. We did not find a significant linear model of BBB K trans versus age for VCID. For healthy controls, the model was K trans = 0.0014 + 0.0002 × age, which was significant (p = 0.046). VCID patients showed a reduction in BCSFB K trans compared to healthy controls (p = 0.01). Combining NAA, CSF MMP3, and K trans in a clustering analysis separated patients into groups. Conclusion: These results suggest that BBB K trans in VCID is dynamic and BCSFB K trans reduced by age. By combining inflammatory biomarkers with BBB K trans data, it is possible to separate VCID patients into distinct groups with different underlying pathologies.

Ulinastatin modulates NLRP3 inflammasome pathway in PTZ-induced epileptic mice: A potential mechanistic insight.

Objective: The NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome-driven immune-inflammatory response has been shown to play a critical role in epilepsy progression across multiple studies. While Ulinastatin (UTI), an immunomodulatory agent known to target the NLRP3 pathway in neurological disorders, its implications in epilepsy have not been extensively studied. This investigation aims to explore UTI's role and underlying mechanisms in epilepsy. Methods: To assess UTI's effects on epilepsy severity, neuroinflammation, and BBB integrity, a pentylenetetrazole (PTZ)-induced epilepsy model in mice and a co-culture system involving BV2 and HT22 cells stimulated by lipopolysaccharide (LPS) and ATP were employed. Techniques utilized included qPCR, Western blotting, ELISA, immunohistochemistry (IHC) staining, Evans Blue dye extravasation, glutamate assays, the Morris water maze, and Annexin V apoptosis assays. Results: In the PTZ model, UTI administration led to a substantial decrease in seizure intensity and susceptibility, inhibited NLRP3 inflammasome activation, reduced neuroinflammatory interactions, lowered hippocampal and systemic inflammatory mediator levels, and improved cognitive performance. Furthermore, UTI upregulated claudin-5 expression, a tight junction protein in the endothelium, and diminished Evans Blue dye leakage, indicating improved BBB integrity. In BV2 and HT22 cell co-culture models, UTI exerted neuroprotective effects by mitigating microglia-mediated neurotoxicity and fostering neuronal recovery. Conclusions: The findings demonstrate that UTI exerts transformative regulatory effects on the NLRP3 inflammasome in epilepsy models. This intervention effectively suppresses neuroinflammation, lessens seizure severity and susceptibility, and ameliorates epilepsy-related BBB dysfunction and cognitive impairments.

Sex-dependent temporal changes in astrocyte-vessel interactions following diffuse traumatic brain injury in rats.

Traumatic brain injury (TBI) is associated with diffuse axonal injury (DAI), a primary pathology linked to progressive neurodegeneration and neuroinflammation, including chronic astrogliosis, which influences long-term post-TBI recovery and morbidity. Sex-based differences in blood-brain barrier (BBB) permeability increases the risk of accelerated brain aging and early-onset neurodegeneration. However, few studies have evaluated chronic time course of astrocytic responses around cerebrovascular in the context of aging after TBI and sex dependence. We observed increased glial fibrillary acidic protein (GFAP)-labeled accessory processes branching near and connecting with GFAP-ensheathed cortical vessels, suggesting a critical nuance in astrocyte-vessel interactions after TBI. To quantify this observation, male and female Sprague Dawley rats (∼3 months old, n = 5-6/group) underwent either sham surgery or midline fluid percussion injury. Using immunohistochemical analysis, we quantified GFAP-labeled astrocyte primary and accessory processes that contacted GFAP-ensheathed vessels in the somatosensory barrel cortex at 7, 56, and 168 days post-injury (DPI). TBI significantly increased GFAP-positive primary processes at 7 DPI (P < 0.01) in both sexes. At 56 DPI, these vessel-process interactions remained significantly increased exclusively in males (P < 0.05). At 168 DPI, both sexes showed a significant reduction in vessel-process interactions compared to 7 DPI (P < 0.05); however, a modest but significant injury effect reemerged in females (P < 0.05). A similar sex-dependent pattern in the number of accessory processes provides novel evidence of long-term temporal changes in astrocyte-vessel interactions. TBI-induced changes in astrocyte-vessel interactions may indicate chronic BBB vulnerability and processes responsible for early onset vascular and neurodegenerative pathology.

From blood to brain: Exploring the role of fibrinogen in the pathophysiology of depression and other neurological disorders.

Recent findings indicate that fibrinogen, a protein involved in blood clotting, plays a significant role in neuroinflammation and mood disorders. Elevated fibrinogen levels are consistently observed in individuals with depression, potentially contributing to microglial activation. This could impair fibrinolysis and contribute to a pro-inflammatory environment in the brain. This neuroinflammatory response can impair neuroplasticity, a key process for learning, memory, and mood regulation. Fibrinogen may also indirectly influence neurotransmitters like serotonin, which play a vital role in mood regulation. Furthermore, fibrinogen's interaction with astrocytes may trigger a cascade of events leading to demyelination, a process where the protective sheath around nerve fibers deteriorates. This can disrupt communication within the nervous system and contribute to depression symptoms. Intriguingly, targeting fibrinogen or related pathways holds promise for therapeutic interventions. For instance, modulating PAI-1 (Plasminogen activator inhibitor-1) activity or inhibiting fibrinogen's interaction with brain cells could be potential strategies. This review explores the multifaceted relationship between fibrinogen and neurological disorders with a focus on depression highlighting its potential as a therapeutic target. Further research is necessary to fully elucidate the mechanisms underlying this association and develop effective therapeutic strategies targeting the fibrinolytic system for mood disorders.

First-line zorifertinib for EGFR-mutant non-small cell lung cancer with central nervous system metastases: The phase 3 EVEREST trial.

BACKGROUND: Zorifertinib (AZD3759), an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) with high blood-brain barrier penetration capability, demonstrated promising intracranial and systemic antitumor activity in phase 1 and 2 studies in central nervous system (CNS)-metastatic patients. METHODS: In this phase 3 EVEREST trial (ClinicalTrials.gov: NCT03653546), patients with EGFR-sensitizing mutations, advanced treatment-naive non-small cell lung cancer (NSCLC), and non-irradiated symptomatic or asymptomatic CNS metastases were randomized (1:1) to zorifertinib or first-generation EGFR-TKI (gefitinib or erlotinib; control). The primary endpoint was blinded independent central review (BICR)-assessed progression-free survival (PFS) per RECIST1.1. FINDINGS: Overall, 439 patients were randomized (zorifertinib n = 220; control n = 219). Most patients had the EGFR L858R mutation (55%) or >3 CNS lesions (54%). Median PFS was significantly longer with zorifertinib versus control (9.6 versus 6.9 months; hazard ratio [HR], 0.719; 95% confidence interval [CI], 0.580-0.893; p = 0.0024). Zorifertinib significantly prolonged intracranial PFS versus control (BICR per modified RECIST1.1: HR, 0.467; 95% CI, 0.352-0.619; investigator per RANO-BM: HR, 0.627; 95% CI, 0.466-0.844). Overall survival (OS) was immature; the estimated median OS was 37.3 months with zorifertinib and 31.8 months with control (HR, 0.833; 95% CI, 0.524-1.283) in patients subsequently treated with third-generation EGFR-TKIs. Safety profiles were consistent with previously reported data for zorifertinib. CONCLUSIONS: Zorifertinib significantly improved systemic and intracranial PFS versus first-generation EGFR-TKIs; adverse events were manageable. Sequential use of zorifertinib and third-generation EGFR-TKIs showed the potential to prolong patients' survival. The results favor zorifertinib as a novel, well-validated first-line option for CNS-metastatic patients with EGFR-mutant NSCLC. FUNDING: This work was funded by Alpha Biopharma (Jiangsu) Co., Ltd., China.

Changes in S100 calcium-binding protein ß (S100ß) and cognitive function from pre- to post-chemotherapy among women with breast cancer.

Many patients with cancer experience cancer-related cognitive decline (CRCD). Previous studies have shown that elevated S100ß, a calcium-binding protein commonly found in glial cells, can exhibit neurotoxic effects, including disruption of the blood-brain barrier (BBB). We studied changes in S100ß levels in patients with breast cancer receiving chemotherapy, and the relationship to changes in cognitive function. A total of 505 women with breast cancer (mean (sd) age; 53.4 (53.6)) and 336 age-matched controls without cancer (52.8 (10.3)) were included from a nationwide study as part of the National Cancer Institute Community Oncology Research Program (NCORP). Both groups provided blood samples and completed neurocognitive assessments within 7 days before the patients with breast cancer received their first chemotherapy dose (pre-chemotherapy; T1) and within 1 month of their last chemotherapy administration (post-chemotherapy; T2). Utilizing a linear mixed model, multivariate linear regressions, and Spearman rank correlations (rs), we investigated longitudinal changes in serum S100ß concentrations and their relationships to changes in neurocognitive outcomes over time. We observed an increase in S100ß for patients with breast cancer (p = 0.002), but not for controls without cancer over time (p = 0.683). Additionally, we identified subtle relationships between increases in serum S100ß and worsening in cognitive performance on the Backward Counting test (rs = 0.11, p = 0.041) and self-reported FACT-Cog Perceived Cognitive Abilities (rs = -0.10, p = 0.025). Regression analyses adjusted for age, race, body-mass index (BMI), education, menopausal status, anxiety, and depression revealed a trend remained for the relationship of S100ß with Backward Counting. In conclusion, we found that patients with breast cancer experience a significant increase in concentration of serum S100ß over the course of chemotherapy. This increase is correlated with worsening in some neurocognitive outcomes from pre-to post-chemotherapy, with trending results remaining following adjustment for covariates.

Novel Treatments for Brain Tumors.

The blood-brain barrier and knowledge gaps in tumor biology remain significant obstacles to the development of effective treatments for brain tumors. The identification of shared molecular and genetic pathways that contribute to tumorigenesis in both dogs and people has been key to the discovery and translation of targeted pharmacologic and biologic therapies. Treatment approaches often utilize targeted or multifunctional antitumor agents, such as nanocarriers, molecularly targeted agents, immunotherapeutics, and oncolytic viruses in combination with alternative therapeutic delivery strategies. The article discusses about various treatments albeit none of the treatments discussed here are widely available or approved for clinical use.

High-Density Lipoprotein Mimetic Peptide 4F Reduces Toxic Amyloid-Beta Exposure to the Blood-Brain Barrier Endothelium in Alzheimer's Disease Transgenic Mice.

Aß accumulation in the blood-brain barrier (BBB) endothelium, which lines the cerebrovascular lumen, is a significant contributor to cerebrovascular dysfunction in Alzheimer's disease (AD). Reduced high-density lipoprotein (HDL) levels are associated with increased AD risk, and the HDL mimetic peptide 4F has been developed as a promising therapeutic agent to improve cerebrovascular health in AD. In this study, we evaluated the impact of 4F on 125I-Aß42 blood-to-brain distribution using dynamic SPECT/CT imaging in both wild-type and APP/PS1 transgenic mice. Graphical analysis of the imaging data demonstrated that 4F significantly reduced the blood-to-brain influx rate in wild-type mice and the distribution of 125I-Aß42 in the BBB endothelium in APP/PS1 mice. To elucidate the molecular mechanisms underlying the effect of 4F, we evaluated its impact on the p38 pathway and its role in mediating Aß42 trafficking in human BBB endothelial cell monolayers. Treatment with 4F significantly decreased Aß42 induced p38 activation in BBB endothelial cells. Furthermore, inhibition of p38 kinase significantly reduced endothelial accumulation of fluorescence-labeled Aß42 and luminal-to-abluminal permeability across the cell monolayer. While our previous publication has hinted at the potential of 4F to reduce Aß accumulation in the brain parenchyma, the current findings demonstrated the protective effect of 4F in reducing Aß42 accumulation in the BBB endothelium of AD transgenic mice. These findings revealed the impact of a clinically tested agent, the HDL mimetic peptide 4F, on Aß exposure to the BBB endothelium and offer novel mechanistic insights into potential therapeutic strategies to treat cerebrovascular dysfunction in AD.

Atomically precise Fluorescent Gold Nanocluster as a barrier-permeable and brain-specific imaging probe.

Photonic nanomaterials play a crucial role in facilitating the necessary signal for optical brain imaging, presenting a promising avenue for early diagnosis of brain-related disorders. However, the blood-brain barrier (BBB) presents a significant challenge, blocking the entry of most molecules or materials from the bloodstream into the brain. To overcome this, photonic nanocrystals in the form of gold clusters (LAuC) with size less than 3nm, have been developed, with Levodopa conjugated to LAuC (Dop@LAuC) for targeted brain imaging. Dop@LAuC crosses the BBB and emits in the near-infrared (NIR) wavelength, enabling real-time optical brain imaging. An in vitro BBB model using brain endothelial cells showed that 50% of Dop@LAuC crossed the barrier within 3 hours, compared to only 10% of LAuC, highlighting the enhanced ability of L-dopa-conjugated gold clusters to penetrate the BBB. In vivo optical imaging in healthy mice further confirmed the material's efficacy to cross BBB without compromising the barrier integrity.

Neurological effects of carbon quantum dots on zebrafish: A review.

Fluorescent carbon dots have emerged as promising nanomaterials for various applications, including bioimaging, food safety detection and drug delivery. However, their potential impact on neurological systems, especially in-vivo models, remains a critical area of investigation. This review focuses on the neurological effects of carbon dots and carbon quantum dots on zebrafish, an established vertebrate model with a conserved central nervous system. Recent studies have demonstrated the efficient uptake and distribution of carbon dots in zebrafish tissues, with a particular affinity for neural tissues. The intricate neural architecture of zebrafish allows for the precise examination of behavioral changes and neurodevelopmental alterations induced by fluorescent carbon dots. Neurotoxicity assessments reveal both short-term and long-term effects, ranging from immediate behavioral alterations to subtle changes in neuronal morphology. The review discusses potential mechanisms underlying these effects highlights the need for standardized methodologies in assessing neurological outcomes and emphasizes the importance of ethical considerations in nanomaterial research. As the field of nanotechnology continues to advance, a comprehensive understanding of the impact of fluorescent carbon dots on neurological function in zebrafish is crucial for informing safe and sustainable applications in medicine and beyond.