Nanomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 4
Published: Jan. 28, 2025
KEYWORDS: Strokenanotherapynanomedicinenanoparticledrug deliverytargeted therapyinflammationoxidative stress
Language: Английский
Bioactive Materials, Journal Year: 2023, Volume and Issue: 29, P. 230 - 240
Published: July 18, 2023
The neuroinflammatory responses following ischemic stroke cause irreversible nerve cell death. Cell free-double strand DNA (dsDNA) segments from tissue debris are engulfed by microglia and sensed their cyclic GMP-AMP synthase (cGAS), which triggers robust activation of the innate immune stimulator interferon genes (STING) pathway initiate chronic inflammatory cascade. decomposition immunogenic dsDNA inhibition STING synergistic immunologic targets for ameliorating neuroinflammation. To combine anti-inflammatory strategies elimination, we constructed a DNase-mimetic artificial enzyme loaded with C-176. Nanoparticles self-assembled amphiphilic copolymers (P[CL35-b-(OEGMA20.7-co-NTAMA14.3)]), C-176, Ce4+ is coordinated nitrilotriacetic acid (NTA) group to form corresponding catalytic structures. Our work developed new nano-drug that balances cGAS-STING axis enhance therapeutic impact combining DNase-memetic inhibitor synergistically. In conclusion, it novel approach modulating central nervus system (CNS) signaling pathways improving prognosis.
Language: Английский
Citations
22
Aging and Disease, Journal Year: 2023, Volume and Issue: unknown, P. 0 - 0
Published: Jan. 1, 2023
Blood-brain barrier (BBB) damage is the main pathological basis for acute ischemic stroke (AIS)-induced cerebral vasogenic edema and hemorrhagic transformation (HT). Glial cells, including microglia, astrocytes, oligodendrocyte precursor cells (OPCs)/oligodendrocytes (OLs) play critical roles in BBB protection. Recent evidence indicates that immune also have an important role damage, HT. Therefore, regulating crosstalk between glial would hold promise to alleviate AIS-induced damage. In this review, we first introduce of glia pericytes, protection after AIS, emphasizing polarization, inflammatory response other cells. We then describe cell-derived exosomes AIS. Next, specifically discuss Finally, propose could be a potential target alleviating AIS some molecular targets strategies by
Language: Английский
Citations
22
Advanced Science, Journal Year: 2024, Volume and Issue: 11(17)
Published: March 5, 2024
Precise and efficient regulation of microglia is vital for ischemic stroke therapy prognosis. The infiltration neutrophils into the brain provides opportunities regulatory drugs across blood-brain barrier, while hindered by neutrophil extracellular traps (NETs) targeted delivery intracerebral to microglia. This study reports an hijacking nanoplatform (referred as APTS) A151 (a telomerase repeat sequence) without generation NETs. In middle cerebral artery occlusion (MCAO) mouse model, efficiency tissues increases fourfold. APTS dramatically reduces formation NETs 2.2-fold via reprogramming NETosis apoptosis in a reactive oxygen species scavenging-mediated citrullinated histone 3 inhibition pathway. Noteworthy, within repackaged apoptotic bodies following death pattern reprogramming, which, when engulfed microglia, polarizes anti-inflammatory M2 phenotype. After four times treatment, infarction area group decreases 5.1-fold. Thus, feasible, efficient, practical drug approach reshaping immune microenvironment treating disorders central nervous system.
Language: Английский
Citations
8
Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: 13(16)
Published: Feb. 7, 2024
Abstract High reactive oxygen species (ROS) levels in tumor microenvironment (TME) impair both immunogenic cell death (ICD) efficacy and T activity. Furthermore, escapes immunosurveillance via programmed death‐1/programmed ligand‐1 (PD‐L1) signal, the insufficient intracellular hydrogen peroxide weakens ferroptosis efficacy. To tackle above issues, a glutathione (GSH)/ROS/pH triple‐responsive prodrug nanomedicine that encapsulates Fe 2 O 3 nanoparticle electrostatic interaction is constructed for magnetic resonance imaging (MRI)‐guided multi‐mode theranostics with chemotherapy/ferroptosis/immunotherapy. The diselenide bond consumes ROS TME to increase cells ICD efficacy, cleavage of which facilitates PD‐L1 antagonist D peptide release block immune checkpoint. After internalization, released acidic endosome MRI simultaneously lipid peroxides generation ferroptosis. Doxorubicin cleaved from polymers condition high GSH level accompanied by ICD, potentiates NADPH oxidase mediated H self‐generation. In vivo results indicate nanoplatform strengthens induces cytotoxic lymphocytes proliferation, inhibits 4T1 regression metastasis, prolongs survival median. all, new strategy proposed strengthening activity cascade as well checkpoint blockade effective immunotherapy.
Language: Английский
Citations
7
Medicinal Research Reviews, Journal Year: 2024, Volume and Issue: 44(6), P. 2793 - 2824
Published: July 19, 2024
Nanoparticles (NPs) that target multiple transport mechanisms facilitate targeted delivery of active therapeutic agents to the central nervous system (CNS) and improve efficacy across blood-brain barrier (BBB). CNS nanotherapeutics mostly neurons endothelial cells, however, microglial immune cells are first line defense against neuronal damage brain infections. Through triggering release inflammatory cytokines, chemokines proteases, microglia can however precipitate neurological damage-a significant factor in neurodegenerative diseases. Thus, inhibitory attracting much attention among those researching developing novel treatments for disorders. The most established inhibitors investigated date resveratrol, curcumin, quercetin, minocycline. there is great interest bypass or easily cross BBB. One such approach use modified-nanocarriers as, for, of, wider CNS. For inhibition, polymeric NPs preferred vehicles choice. Here, we summarize immunologic neuroinflammatory role microglia, inhibitor agents, challenges drug delivery, explored inhibition date. We also discuss applications currently considered "most useful" microglial-inhibitor CNS-related
Language: Английский
Citations
7
Nano Letters, Journal Year: 2024, Volume and Issue: 24(17), P. 5214 - 5223
Published: April 22, 2024
Stroke is a leading cause of global mortality and severe disability. However, current strategies used for treating ischemic stroke lack specific targeting capabilities, exhibit poor immune escape ability, have limited drug release control. Herein, we developed an ROS-responsive nanocarrier targeted delivery the neuroprotective agent rapamycin (RAPA) to mitigate brain damage. The consisted sulfated chitosan (SCS) polymer core modified with boronic ester enveloped by red blood cell membrane shell incorporating homing peptide. When encountering high levels intracellular ROS in tissues, SCS combined RAPA from nanoparticle disintegration facilitates effective microglia polarization and, turn, maintains blood–brain barrier integrity, reduces cerebral infarction, promotes neurovascular remodeling mouse model involving transient middle artery occlusion (tMCAO). This work offers promising strategy treat therapy.
Language: Английский
Citations
6
Biomaterials Research, Journal Year: 2024, Volume and Issue: 28
Published: Jan. 1, 2024
Intervertebral discs (IVDs) have a limited self-regenerative capacity and current strategies for IVD regeneration are unsatisfactory. Recent studies showed that small extracellular vesicles derived from M2 macrophage cells (M2-sEVs) inhibited inflammation by delivery of various bioactive molecules to recipient cells, which indicated M2-sEVs may offer therapeutic strategy the repair IVDs. Herein, we investigated roles mechanisms on regeneration. The in vitro results demonstrated pyroptosis, preserved cellular viability, promoted migration nucleus pulposus (NPCs). Bioinformatics analysis verification experiments microRNA (miR) expression miR-221-3p was highly expressed M2-sEVs. mechanism action explored pyroptosis NPCs through transfer miR-221-3p, suppressed levels phosphatase tensin homolog NOD-, LRR-, pyrin domain-containing protein 3. Moreover, fabricated decellularized ECM-hydrogel (dECM) sustained release M2-sEVs, exhibited biocompatibility controlled properties. vivo revealed dECM-hydrogel containing (dECM/M2-sEVs) delayed degeneration intervertebral disc (IDD) models. In addition demonstrating promising IDD, this study provided valuable data furthering understanding
Language: Английский
Citations
6
Advanced Healthcare Materials, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 7, 2024
Abstract Overproduction of reactive oxygen species (ROS) during reperfusion in ischemic stroke (IS) severely impedes neuronal survival and results high rates morbidity disability. The effective blood‐brain barrier (BBB) penetration brain delivery antioxidative agents remain the biggest challenge treating reperfusion‐induced cerebrovascular neural injury. In this study, a metal‐organic framework (MOF) nanozyme (MIL‐101‐NH 2 (Fe/Cu)) with ROS scavenging activities to encapsulate neuroprotective agent rapamycin is fabricated decorating exterior BBB‐targeting protein ligands (transferrin), thereby realizing enhanced drug retention controlled release within lesions for synergistic treatment IS. Through receptor‐mediated transcellular pathway, transferrin‐coated MOF nanoparticles achieved efficient transport across BBB targeted accumulation at cerebral injury site mice middle artery occlusion/reperfusion (MCAO/R), wherein nanocarrier exhibited catalytic decomposition into O H ‐responsive release. By its BBB‐targeting, antioxidative, anti‐inflammatory, antiapoptotic properties, nanosystem addressed multiple pathological factors IS realized remarkable effects, leading substantial reduction infarction volume accelerated recovery nerve functions MCAO/R mouse model. This MOF‐based nanomedicine provides valuable design principles therapy multi‐mechanism synergies.
Language: Английский
Citations
5
European journal of medical research, Journal Year: 2022, Volume and Issue: 27(1)
Published: Nov. 4, 2022
Angiogenesis is a vital biological process involving blood vessels forming from pre-existing vascular systems. This contributes to various physiological activities, including embryonic development, hair growth, ovulation, menstruation, and the repair regeneration of damaged tissue. On other hand, it essential in treating wide range pathological diseases, such as cardiovascular ischemic rheumatoid arthritis, malignancies, ophthalmic retinal chronic conditions. These diseases disorders are frequently treated by regulating angiogenesis utilizing variety pro-angiogenic or anti-angiogenic agents molecules stimulating suppressing this complicated process, respectively. Nevertheless, many traditional angiogenic therapy techniques suffer lack ability achieve intended therapeutic impact because constraints. disadvantages include limited bioavailability, drug resistance, fast elimination, increased price, nonspecificity, adverse effects. As result, an excellent time for developing pro- substances that might circumvent abovementioned restrictions, followed their efficient use associated with angiogenesis. In recent years, significant progress has been made different fields medicine biology, Around world, multitude research groups investigated several inorganic organic nanoparticles (NPs) had potential effectively modify processes either enhancing process. Many studies into behind NP-mediated well described. article, we also cover application NPs encourage tissue vascularization effects treatment disorders, bone regeneration, peripheral disease, diabetic retinopathy, stroke, post-ischemic injury, age-related macular degeneration, gene delivery-based therapy, protein stem cell cancer may benefit behavior nanostructures system throughout body. addition, accompanying difficulties future applications angiogenesis-related antiangiogenic therapies discussed.
Language: Английский
Citations
20
Annals of Translational Medicine, Journal Year: 2023, Volume and Issue: 11(6), P. 264 - 264
Published: Feb. 8, 2023
The mitochondrion is a crucial organelle for aerobic respiration and energy metabolism. It undergoes dynamic changes, including changes in its shape, function, distribution through fission, fusion, movement. Under normal conditions, mitochondrial dynamics are homeostasis. However, once the balance upset, nervous system, which has high metabolic demands, will most likely be affected. Recent studies have shown that imbalance of involved occurrence development various neurological diseases. whether regulation can used to treat diseases still unclear. We aimed comprehensively analyze potential role treatment diseases.A comprehensive literature review was carried out understand mechanisms applications based on available PubMed, Web Science, Google Scholar.This discusses molecular related expounds upon neurodegenerative diseases, epilepsy, cerebrovascular disease, brain tumors. Several clinically tested drugs with fewer side effects been improve system function diseases.Disorders cause Elucidation inform new therapeutic targets strategies Dynamin-related protein 1 (Drp1), as highly relevant dynamics, might target treating future.
Language: Английский
Citations
11