An overview of in vitro 3D models of the blood-brain barrier as a tool to predict the in vivo permeability of nanomedicines

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 196, P. 114816 - 114816

Published: March 30, 2023

The blood-brain barrier (BBB) prevents efficient drug delivery to the central nervous system. As a result, brain diseases remain one of greatest unmet medical needs. Understanding tridimensional structure BBB helps gain insight into pathology and contributes development novel therapies for diseases. Therefore, 3D models with an ever-growing sophisticated complexity are being developed closely mimic human neurovascular unit. Among these models, hydrogel-, spheroid- organoid-based static have been developed, so microfluidic-based BBB-on-a-chip models. different preclinical BBB, both in health disease, here reviewed, from their application permeability testing nanomedicines across discussing advantages disadvantages each model. validation data vivo is also discussed those cases where provided.

Language: Английский

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Immunotherapy for glioblastoma: current state, challenges, and future perspectives

Cellular and Molecular Immunology, Journal Year: 2024, Volume and Issue: 21(12), P. 1354 - 1375

Published: Oct. 15, 2024

Glioblastoma (GBM) is an aggressive and lethal type of brain tumor in human adults. The standard care offers minimal clinical benefit, most GBM patients experience recurrence after treatment. In recent years, significant advancements have been made the development novel immunotherapies or other therapeutic strategies that can overcome immunotherapy resistance many advanced cancers. However, benefit immune-based treatments limited because unique immune profiles, cell heterogeneity, immunosuppressive microenvironment. this review, we present a detailed overview current immunotherapeutic discuss challenges potential molecular mechanisms underlying GBM. Furthermore, provide in-depth discussion regarding GBM, which will likely require combination therapies.

Language: Английский

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The Role of Microglia in Brain Metastases: Mechanisms and Strategies

Aging and Disease, Journal Year: 2024, Volume and Issue: 15(1), P. 169 - 169

Published: Jan. 1, 2024

Brain metastases and related complications are one of the major fatal factors in cancer. Patients with breast cancer, lung melanoma at a high risk developing brain metastases. However, mechanisms underlying metastatic cascade remain poorly understood. Microglia, resident macrophages parenchyma, involved multiple processes associated metastasis, including inflammation, angiogenesis, immune modulation. They also closely interact cancer cells, astrocytes, other cells. Current therapeutic approaches against cancers, small-molecule drugs, antibody-coupled drugs (ADCs), immune-checkpoint inhibitors (ICIs), have compromised efficacy owing to impermeability blood-brain barrier (BBB) complex microenvironment. Targeting microglia is strategies for treating In this review, we summarize multifaceted roles highlight them as potential targets future interventions.

Language: Английский

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Immunotherapeutic Strategies for the Treatment of Glioblastoma: Current Challenges and Future Perspectives

Cancers, Journal Year: 2024, Volume and Issue: 16(7), P. 1276 - 1276

Published: March 25, 2024

Despite decades of research and the best up-to-date treatments, grade 4 Glioblastoma (GBM) remains uniformly fatal with a patient median overall survival less than 2 years. Recent advances in immunotherapy have reignited interest utilizing immunological approaches to fight cancer. However, current immunotherapies so far not met anticipated expectations, achieving modest results their journey from bench bedside for treatment GBM. Understanding intrinsic features GBM is crucial importance development effective antitumoral strategies improve life expectancy conditions. In this review, we provide comprehensive overview distinctive characteristics that significantly influence conventional therapies immune-based approaches. Moreover, present an immunotherapeutic currently undergoing clinical evaluation treatment, specific emphasis on those advancing phase 3 studies. These encompass immune checkpoint inhibitors, adoptive T cell therapies, vaccination (i.e., RNA-, DNA-, peptide-based vaccines), virus-based Finally, explore novel innovative future prospects field

Language: Английский

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Principles in the Management of Glioblastoma

Genes, Journal Year: 2024, Volume and Issue: 15(4), P. 501 - 501

Published: April 17, 2024

Glioblastoma, the most aggressive and common malignant primary brain tumour, is characterized by infiltrative growth, abundant vascularization, clinical evolution. Patients with glioblastoma often face poor prognoses, a median survival of approximately 15 months. Technological progress subsequent improvement in understanding pathophysiology these tumours have not translated into significant achievements therapies or outcomes for patients. Progress molecular profiling has yielded new omics data more refined classification glioblastoma. Several typical genetic epigenetic alterations include mutations genes regulating receptor tyrosine kinase (RTK)/rat sarcoma (RAS)/phosphoinositide 3-kinase (PI3K), p53, retinoblastoma protein (RB) signalling, as well mutation isocitrate dehydrogenase (IDH), methylation O6-methylguanine-DNA methyltransferase (MGMT), amplification epidermal growth factor vIII, codeletion 1p/19q. Certain microRNAs, such miR-10b miR-21, also been identified prognostic biomarkers. Effective treatment options are limited. Surgery, radiotherapy, alkylating agent chemotherapy remain pillars treatment. Only promoter gene MGMT predicts benefit from temozolomide it guides choice first-line elderly targeted strategies based on tumour-intrinsic dominant signalling pathways antigenic tumour profiles under investigation trials. This review explores potential biomarkers that could be deployed analytical tools diagnosis prognostication Recent advancements treating discussed, along liquid biopsies to advance personalized medicine field glioblastoma, highlighting challenges promises future.

Language: Английский

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Nanoparticle-Based Combinational Strategies for Overcoming the Blood-Brain Barrier and Blood-Tumor Barrier

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 2529 - 2552

Published: March 1, 2024

Abstract: The blood-brain barrier (BBB) and blood-tumor (BTB) pose substantial challenges to efficacious drug delivery for glioblastoma multiforme (GBM), a primary brain tumor with poor prognosis. Nanoparticle-based combinational strategies have emerged as promising modalities overcome these barriers enhance penetration into the parenchyma. This review discusses various nanoparticle-based combinatorial approaches that combine nanoparticles cell-based delivery, viral focused ultrasound, magnetic field, intranasal permeability across BBB BTB. Cell-based involves using engineered cells carriers nanoparticles, taking advantage of their intrinsic migratory homing capabilities facilitate transport therapeutic payloads Viral uses vectors deliver genes or specific within GBM microenvironment. Focused coupled microbubbles can temporarily disrupt increase permeability. Magnetic field-guided exploits targeted under an external field. Intranasal offers minimally invasive avenue bypass agents directly via olfactory trigeminal pathways. By combining strategies, synergistic effects efficiency, improve efficacy, reduce off-target effects. Future research should focus on optimizing nanoparticle design, exploring new combination advancing preclinical clinical investigations promote translation therapies GBM. Keywords: glioblastoma, barrier, nanoparticle, strategy, ultrasound-wave,

Language: Английский

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Advancing neurological disorders therapies: Organic nanoparticles as a key to blood-brain barrier penetration

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: 670, P. 125186 - 125186

Published: Jan. 8, 2025

The blood-brain barrier (BBB) plays a vital role in protecting the central nervous system (CNS) by preventing entry of harmful pathogens from bloodstream. However, this also presents significant obstacle when it comes to delivering drugs for treatment neurodegenerative diseases and brain cancer. Recent breakthroughs nanotechnology have paved way creation wide range nanoparticles (NPs) that can serve as carriers diagnosis therapy. Regarding their promising properties, organic NPs potential be used effective drug delivery across BBB based on recent advancements. These remarkable ability penetrate using various mechanisms. This review offers comprehensive examination intricate structure distinct properties BBB, emphasizing its crucial function preserving balance regulating transport ions molecules. disruption conditions such stroke, Alzheimer's disease, Parkinson's disease highlights importance developing creative approaches drugs. Through encapsulation therapeutic molecules precise targeting processes vasculature, NP formulations present hopeful strategy improve BBB. We explore changes pathological investigate factors affect successful into brain. In addition, we most systems associated with shown positive results treating ischemic disorders. opens up new possibilities nanotechnology-based therapies cerebral diseases.

Language: Английский

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Macrophage membrane-camouflaged pure-drug nanomedicine for synergistic chemo- and interstitial photodynamic therapy against glioblastoma

Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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New Advances in Biomedical Application of Polymeric Micelles

Pharmaceutics, Journal Year: 2022, Volume and Issue: 14(8), P. 1700 - 1700

Published: Aug. 15, 2022

In the last decade, nanomedicine has arisen as an emergent area of medicine, which studies nanometric systems, namely polymeric micelles (PMs), that increase solubility and stability encapsulated drugs. Furthermore, their application in dermal drug delivery is also relevant. PMs present unique characteristics because core-shell architecture. They are colloidal dispersions amphiphilic compounds, self-assemble aqueous medium, giving a structure-type core-shell, with hydrophobic core (that can encapsulate drugs), hydrophilic shell, works stabilizing agent. These features offer adequate steric protection determine hydrophilicity, charge, length, surface density properties. due to small size, be absorbed by intestinal mucosa drug, they transport bloodstream until therapeutic target. Moreover, improve pharmacokinetic profile high load capacity, synthesized reproducible, easy, low-cost method. silico approaches have been explored physicochemical properties PMs. Based on this, computer-aided strategy was developed validated enable poorly soluble drugs established critical parameters maximize loading, formulation stability, tumor exposure. Poly(2-oxazoline) (POx)-based display unprecedented loading concerning water-insoluble over 60 incorporated POx Among various stimuli, pH temperature most widely studied for enhanced release at site action. Researchers focusing dual (pH temperature) responsive controlled improved systems mainly evaluated cancer therapy certain malignancies cause slight decrease extracellular around site. This review compilation updated applications PMs, such based Pluronics®, micelleplexes Pox-based several biomedical applications.

Language: Английский

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Digging the intercellular crosstalk via extracellular vesicles: May exosomes be the drug delivery solution for target glioblastoma?

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 358, P. 98 - 115

Published: April 29, 2023

Glioblastoma (GBM) is an adult's most aggressive brain tumor. The advances in molecular pathology and cell signaling pathways have deepened researchers' understanding of intercellular communication mechanisms that can induce tumor progression, namely the release extracellular vesicles. Exosomes are small vesicles various biological fluids released by almost all cells, thus carrying biomolecules specific to their parental cell. Several pieces evidence indicate exosomes mediate microenvironment cross blood-brain barrier (BBB), valuable tools for diagnostic therapeutic applications under scope diseases such as tumors. This review aims resume several characteristics interplay between glioblastoma exosomes, describing highlight studies demonstrate role GBM potential non-invasive diagnoses approaches, namely, nanocarriers drug or gene delivery cancer vaccines.

Language: Английский

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