Engineered nanomaterials that exploit blood-brain barrier dysfunction for delivery to the brain

Wu, Jason; Hernandez, Yazmin; Miyasaki, Katelyn; Kwon, Ester J.

doi:10.1016/j.addr.2023.114820

Cited by 19 publications

(12 citation statements)

References 255 publications

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“…For such treatments to become commonplace, one of the main areas of improvement is in traversing the BBB and delivering APIs directly to the relevant site of action. This will require a greater understanding of the mechanisms of nanoparticle permeation into the brain, including the importance of NP composition, size, charge, and shape, engineering the adsorbed biomolecular corona to not obstruct NP targeting, targeting the proper cell type once the NPs enter the brain, design of better-targeting moieties on the external surface of nanoparticles through such processes as in vivo phage display screening, exact API release timelines that induce desired outcomes, and, importantly, a more complete understanding of how to modulate glia to produce desired clinical outcomes ( Salvati et al, 2013 ; Mann et al, 2016 ; Furtado et al, 2018 ; Waggoner et al, 2023 ; Wu et al, 2023 ). More personalized therapies can be envisioned, where each individual may respond to NPs differently.…”

Section: Discussionmentioning

confidence: 99%

Nanomaterial payload delivery to central nervous system glia for neural protection and repair

Saksena,

Hamilton,

Gilbert

et al. 2023

Front. Cell. Neurosci.

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Central nervous system (CNS) glia, including astrocytes, microglia, and oligodendrocytes, play prominent roles in traumatic injury and degenerative disorders. Due to their importance, active pharmaceutical ingredients (APIs) are being developed to modulate CNS glia in order to improve outcomes in traumatic injury and disease. While many of these APIs show promise in vitro, the majority of APIs that are systemically delivered show little penetration through the blood–brain barrier (BBB) or blood-spinal cord barrier (BSCB) and into the CNS, rendering them ineffective. Novel nanomaterials are being developed to deliver APIs into the CNS to modulate glial responses and improve outcomes in injury and disease. Nanomaterials are attractive options as therapies for central nervous system protection and repair in degenerative disorders and traumatic injury due to their intrinsic capabilities in API delivery. Nanomaterials can improve API accumulation in the CNS by increasing permeation through the BBB of systemically delivered APIs, extending the timeline of API release, and interacting biophysically with CNS cell populations due to their mechanical properties and nanoscale architectures. In this review, we present the recent advances in the fields of both locally implanted nanomaterials and systemically administered nanoparticles developed for the delivery of APIs to the CNS that modulate glial activity as a strategy to improve outcomes in traumatic injury and disease. We identify current research gaps and discuss potential developments in the field that will continue to translate the use of glia-targeting nanomaterials to the clinic.

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Section: Discussionmentioning

confidence: 99%

Nanomaterial payload delivery to central nervous system glia for neural protection and repair

Saksena,

Hamilton,

Gilbert

et al. 2023

Front. Cell. Neurosci.

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“…Although the BBB is highly efficient, when compromised due to physical or neurological disorders, UFPs can pass through, increasing the potential toxicological impacts (Figure 1b) (Wu et al, 2023).…”

Section: Environmental Horizonmentioning

confidence: 99%

“…Activation of microglia may produce reactive oxygen species (ROS), causing neuroinflammation (Figure 1a) (Ehsanifar et al., 2021). Although the BBB is highly efficient, when compromised due to physical or neurological disorders, UFPs can pass through, increasing the potential toxicological impacts (Figure 1b) (Wu et al., 2023). Metal‐rich ultrafine particles (UFPs) have been associated with Alzheimer's disease (AD) and Parkinson's disease (PD) as promoters of protein misfolding and aggregation.…”

Section: Blood–brain Barriermentioning

confidence: 99%

Implications of environmental nanoparticles on neurodegeneration

Hermosillo‐Abundis,

Méndez‐Rojas,

Arias‐Carrión

2024

J of Neuroscience Research

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The ubiquity of nanoparticles, sourced from both natural environments and human activities, presents critical challenges for public health. While offering significant potential for innovative biomedical applications—especially in enhancing drug transport across the blood–brain barrier—these particles also introduce possible hazards due to inadvertent exposure. This concise review explores the paradoxical nature of nanoparticles, emphasizing their promising applications in healthcare juxtaposed with their potential neurotoxic consequences. Through a detailed examination, we delineate the pathways through which nanoparticles can reach the brain and the subsequent health implications. There is growing evidence of a disturbing association between nanoparticle exposure and the onset of neurodegenerative conditions, highlighting the imperative for comprehensive research and strategic interventions. Gaining a deep understanding of these mechanisms and enacting protective policies are crucial steps toward reducing the health threats of nanoparticles, thereby maximizing their therapeutic advantages.

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“…This approach is particularly valuable when optimizing the inherent physicochemical properties of NPs alone proves insufficient to achieve the desired targeting efficiency. Furthermore, NPs have a high surface-to-volume ratio, which is ideal for functionalization with ligands or active functional groups to enhance BBB targeting [17,52]. Strategies to conjugate the NPs with biological or synthetic molecules, or to coat NPs' surfaces with surfactants, have been developed to enhance the binding of NPs with specific BBB endothelial receptors or decrease the level of systemic clearance [53][54][55].…”

Section: Surface Modificationmentioning

confidence: 99%

Blood–Brain Barrier-Targeting Nanoparticles: Biomaterial Properties and Biomedical Applications in Translational Neuroscience

Asimakidou,

Tan,

Zeng

et al. 2024

Pharmaceuticals

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Overcoming the blood–brain barrier (BBB) remains a significant hurdle in effective drug delivery to the brain. While the BBB serves as a crucial protective barrier, it poses challenges in delivering therapeutic agents to their intended targets within the brain parenchyma. To enhance drug delivery for the treatment of neurological diseases, several delivery technologies to circumvent the BBB have been developed in the last few years. Among them, nanoparticles (NPs) are one of the most versatile and promising tools. Here, we summarize the characteristics of NPs that facilitate BBB penetration, including their size, shape, chemical composition, surface charge, and importantly, their conjugation with various biological or synthetic molecules such as glucose, transferrin, insulin, polyethylene glycol, peptides, and aptamers. Additionally, we discuss the coating of NPs with surfactants. A comprehensive overview of the common in vitro and in vivo models of the BBB for NP penetration studies is also provided. The discussion extends to discussing BBB impairment under pathological conditions and leveraging BBB alterations under pathological conditions to enhance drug delivery. Emphasizing the need for future studies to uncover the inherent therapeutic properties of NPs, the review advocates for their role beyond delivery systems and calls for efforts translating NPs to the clinic as therapeutics. Overall, NPs stand out as a highly promising therapeutic strategy for precise BBB targeting and drug delivery in neurological disorders.

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Engineered nanomaterials that exploit blood-brain barrier dysfunction for delivery to the brain

Cited by 19 publications

References 255 publications

Nanomaterial payload delivery to central nervous system glia for neural protection and repair

Nanomaterial payload delivery to central nervous system glia for neural protection and repair

Implications of environmental nanoparticles on neurodegeneration

Blood–Brain Barrier-Targeting Nanoparticles: Biomaterial Properties and Biomedical Applications in Translational Neuroscience

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