The blood–brain barrier: Structure, regulation and drug delivery

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Май 25, 2023

Abstract Blood–brain barrier (BBB) is a natural protective membrane that prevents central nervous system (CNS) from toxins and pathogens in blood. However, the presence of BBB complicates pharmacotherapy for CNS disorders as most chemical drugs biopharmaceuticals have been impeded to enter brain. Insufficient drug delivery into brain leads low therapeutic efficacy well aggravated side effects due accumulation other organs tissues. Recent breakthrough materials science nanotechnology provides library advanced with customized structure property serving powerful toolkit targeted delivery. In-depth research field anatomical pathological study on further facilitates development brain-targeted strategies enhanced crossing. In this review, physiological different cells contributing are summarized. Various emerging permeability regulation crossing including passive transcytosis, intranasal administration, ligands conjugation, coating, stimuli-triggered disruption, overcome obstacle highlighted. Versatile systems ranging organic, inorganic, biologics-derived their synthesis procedures unique physio-chemical properties summarized analyzed. This review aims provide an up-to-date comprehensive guideline researchers diverse fields, offering perspectives system.

Язык: Английский

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Tumor‐Microenvironment‐Responsive Nanomedicine for Enhanced Cancer Immunotherapy

Advanced Science, Год журнала: 2021, Номер 9(1)

Опубликована: Ноя. 19, 2021

Abstract The past decades have witnessed great progress in cancer immunotherapy, which has profoundly revolutionized oncology, whereas low patient response rates and potential immune‐related adverse events remain major clinical challenges. With the advantages of controlled delivery modular flexibility, nanomedicine offered opportunities to strengthen antitumor immune responses sensitize tumor immunotherapy. Furthermore, tumor‐microenvironment (TME)‐responsive been demonstrated achieve specific localized amplification tissue a safe effective manner, increasing immunotherapy reducing side effects simultaneously. Here, recent TME‐responsive for is summarized, responds signals TME, such as weak acidity, reductive environment, high‐level reactive oxygen species, hypoxia, overexpressed enzymes, adenosine triphosphate. Moreover, combine nanomedicine‐based therapy immunotherapeutic strategies overcome each step cancer‐immunity cycle enhance discussed. Finally, existing challenges further perspectives this rising field with hope improved development applications are

Язык: Английский

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Rethinking CRITID Procedure of Brain Targeting Drug Delivery: Circulation, Blood Brain Barrier Recognition, Intracellular Transport, Diseased Cell Targeting, Internalization, and Drug Release

Advanced Science, Год журнала: 2021, Номер 8(9)

Опубликована: Фев. 24, 2021

Abstract The past decades have witnessed great progress in nanoparticle (NP)‐based brain‐targeting drug delivery systems, while their therapeutic potentials are yet to be fully exploited given that the majority of them lost during process. Rational design systems requires a deep understanding entire process along with issues they may encounter. Herein, this review first analyzes typical systemically administrated NPs‐based system and proposes six‐step CRITID cascade: circulation systemic blood, recognizing receptor on blood‐brain barrier (BBB), intracellular transport, diseased cell targeting after entering into parenchyma, internalization by cells, finally release. By dissecting six steps, seeks provide restrict efficiency as well specific requirements guarantee minimal loss at each step. Currently developed strategies used for troubleshooting these reviewed some state‐of‐the‐art features meeting highlighted. cascade can serve guideline designing more efficient systems.

Язык: Английский

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The protein corona hampers the transcytosis of transferrin-modified nanoparticles through blood–brain barrier and attenuates their targeting ability to brain tumor

Biomaterials, Год журнала: 2021, Номер 274, С. 120888 - 120888

Опубликована: Май 18, 2021

Язык: Английский

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Brain co‐delivery of first‐line chemotherapy drug and epigenetic bromodomain inhibitor for multidimensional enhanced synergistic glioblastoma therapy

Exploration, Год журнала: 2022, Номер 2(4)

Опубликована: Апрель 19, 2022

Glioblastoma (GBM) is a central nervous system tumor with poor prognosis due to the rapid development of resistance mono chemotherapy and brain targeted delivery. Chemoimmunotherapy (CIT) combines drugs activators innate immunity that hold great promise for GBM synergistic therapy. Herein, we chose temozolomide, TMZ, epigenetic bromodomain inhibitor, OTX015, further co-encapsulated them within our well-established erythrocyte membrane camouflaged nanoparticle yield ApoE peptide decorated biomimetic nanomedicine (ABNM@TMZ/OTX). Our nanoplatform successfully addressed limitations in brain-targeted drug co-delivery, simultaneously achieved multidimensional enhanced CIT. In mice bearing orthotopic GL261 GBM, treatment ABNM@TMZ/OTX resulted marked inhibition greatly extended survival time little side effects. The pronounced efficacy can be ascribed three key factors: (i) improved nanoparticle-mediated targeting delivery therapeutic agents by blood circulation blood-brain barrier penetration; (ii) inhibited cellular DNA repair TMZ sensitivity cells; (iii) anti-tumor immune responses inducing immunogenic cell death inhibiting PD-1/PD-L1 conjugation leading expression CD4

Язык: Английский

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Cancer cell-mitochondria hybrid membrane coated Gboxin loaded nanomedicines for glioblastoma treatment

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Июль 28, 2023

Abstract Glioblastoma (GBM) remains the most lethal malignant tumours. Gboxin, an oxidative phosphorylation inhibitor, specifically restrains GBM growth by inhibiting activity of F 0 1 ATPase complex V. However, its anti-GBM effect is seriously limited poor blood circulation, brain barrier (BBB) and non-specific tissue/cell uptake, leading to insufficient Gboxin accumulation at sites, which limits further clinical application. Here we present a biomimetic nanomedicine (HM-NPs@G) coating cancer cell-mitochondria hybrid membrane (HM) on surface Gboxin-loaded nanoparticles. An additional design element uses reactive oxygen species responsive polymer facilitate at-site release. The HM camouflaging endows HM-NPs@G with unique features including good biocompatibility, improved pharmacokinetic profile, efficient BBB permeability homotypic dual tumour cell mitochondria targeting. results suggest that achieve circulation (4.90 h versus 0.47 free Gboxin) (7.73% ID/g 1.06% shown Gboxin). Effective inhibition in orthotopic U87MG patient derived X01 stem xenografts female mice extended survival time negligible side effects are also noted. We believe represents promising treatment for tumours potential.

Язык: Английский

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Surface-modified lipid nanocarriers for crossing the blood-brain barrier (BBB): A current overview of active targeting in brain diseases

Colloids and Surfaces B Biointerfaces, Год журнала: 2022, Номер 221, С. 112999 - 112999

Опубликована: Ноя. 2, 2022

The blood-brain barrier (BBB) restricts the access of therapeutic agents to brain, complicating treatment neurological diseases, such as Alzheimer's disease (AD), Parkinson's (PD), multiple sclerosis (MS), glioma, etc. To overcome this limitation and improve drug delivery central nervous system (CNS), potential nanocarriers, including lipid-based nanosystems, has been explored. Through active targeting, surface nanocarriers can be modified with ligands that interact BBB, enhancing their uptake penetration across brain endothelium by different physiological mechanisms, receptor- or transporter-mediated transcytosis. This review seeks provide an overview targeting in delivery, while highlighting functionalized lipid treat diseases. Therefore, first sections, we discuss importance CNS present commonly used for functionalization, well summarize state art most recent relevant studies surface-modified nanosystems developed disorders. Lastly, challenges hindering clinical translation are discussed, critical insights future perspectives outlined. Although some limitations have identified, it is expected upcoming years these will established approach.

Язык: Английский

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Intranasal Delivery of BACE1 siRNA and Rapamycin by Dual Targets Modified Nanoparticles for Alzheimer's Disease Therapy

Small, Год журнала: 2022, Номер 18(30)

Опубликована: Июнь 30, 2022

Abstract Alzheimer's disease (AD), as a progressive and irreversible brain disorder, remains the most universal neurodegenerative disease. No effective therapeutic methods are established yet due to hindrance of blood‐brain barrier (BBB) complex pathological condition AD. Therefore, multifunctional nanocarrier (Rapa@DAK/siRNA) for AD treatment is constructed achieve small interfering RNA β‐site precursor protein (APP) cleaving enzyme‐1 (BACE1 siRNA) rapamycin co‐delivery into brain, based on Aleuria aurantia lectin (AAL) β‐amyploid (Aβ)‐binding peptides (KLVFF) modified PEGylated dendrigraft poly‐ l ‐lysines (DGLs) via intranasal administration. Nasal administration provides an way deliver drugs directly through nose‐to‐brain pathway. AAL, specifically binding L‐fucose located in olfactory epithelium, endows Rapa@DAK/siRNA with high entry efficiency KLVFF peptide Aβ targeting ligand aggregation inhibitor enables nanoparticles bind Aβ, inhibit aggregation, reduce toxicity. Meanwhile, release BACE1 siRNA confirmed expression, promote autophagy, deposition. verified improve cognition transgenic mice after Collectively, potential avenue combination therapy

Язык: Английский

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Manganese-based hollow nanoplatforms for MR imaging-guided cancer therapies

Biomaterials Research, Год журнала: 2022, Номер 26(1)

Опубликована: Июль 6, 2022

Theranostic nanoplatforms integrating diagnostic and therapeutic functions have received considerable attention in the past decade. Among them, hollow manganese (Mn)-based are superior since they combine advantages of structures intrinsic theranostic features Mn

Язык: Английский

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The impact of protein corona on the biological behavior of targeting nanomedicines

International Journal of Pharmaceutics, Год журнала: 2022, Номер 614, С. 121458 - 121458

Опубликована: Янв. 10, 2022

Язык: Английский

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