Transmigration of magnetite nanoparticles across the blood–brain barrier in a rodent model: influence of external and alternating magnetic fields

Gupta, Ruby; Chauhan, Anjali; Kaur, Tashmeen; Kuanr, Bijoy K.; Sharma, Deepika

doi:10.1039/d2nr02210a

Cited by 10 publications

(16 citation statements)

References 64 publications

(101 reference statements)

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“…It has been reported that high-frequency magnetic fields can activate magnetic NPs and in turn induce cell death via cytoskeletal degradation and disruption of the cell cycle at higher particle concentration and longer incubation times . In the present study (low-frequency magnetic fields), the minimal cell viability reduction at 125 μg/mL could be attributed to oxidative stress activities. − At concentrations <125 μg/mL, the combination treatment leaves the healthy cells completely unaffected. Based on these findings, we used 100 μg/mL as the particle concentration to perform endothelial leakiness studies.…”

Section: Resultsmentioning

confidence: 43%

“…50,51 Also, shear stress can cause modulation of the cytoskeleton, intercellular junctions, and vascular permeability. 42 By contrast, magneto- NdFeB magnets (which produce static magnetic fields, ∼500 mT) and PEG-coated magnetite nanocrystals (16 and 33 nm in diameter). 3 The authors proved that magneto-mechanical transduced stress can transiently disrupt endothelial adherens junctions of HUVEC monolayers.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…It has been reported that shear stress, a membrane-transduced stress, provoked by “surface” forces can align endothelial cells with the direction of the stress. , Also, shear stress can cause modulation of the cytoskeleton, intercellular junctions, and vascular permeability . By contrast, magneto-mechanically transduced stress provoked by intracellular “body” forces is different in nature (e.g., directionality), originates within the cells, and is dictated by specific pathways.…”

Section: Resultsmentioning

confidence: 99%

“…Other research groups ,,, investigating different types of VE-cadherin and tight junction disruption approaches reported similar findings on actin filament remodeling and formation of stress fibers. Gupta et al investigated the transmigration of biocompatible magnetite NPs (∼5 nm in diameter) across endothelial layers containing bEnd.3 murine brain endothelial cells (top) and C8-D1A astrocytes (bottom) . Using a transwell model, NP-containing cells were exposed to alternating magnetic fields (335 kHz, ∼20 mT, and 20 min), which led to the damage of the tight junction integrity.…”

Section: Resultsmentioning

confidence: 99%

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Magneto-Mechanical Actuation Induces Endothelial Permeability

Kanber,

Umerah,

Brindley

et al. 2023

ACS Biomater. Sci. Eng.

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Cancer treatment is one of the major health problems that burden our society. According to the American Cancer Society, over 1.9 million new cancer cases and ∼0.6 million deaths from cancer are expected in the US in 2023. Therapeutic targeting is considered to be the gold standard in cancer treatment. However, when a tumor grows beyond a critical size, its vascular system differentiates abnormally and erratically, creating a heterogeneous endothelial barrier that further restricts drug delivery into tumors. While several methods exist, these prompt tumor migration and the appearance of new metastatic sites. Herein, we propose an innovative method based on magneto-mechanical actuation (MMA) to induce endothelial permeability. This method employs FDA-approved PEGylated superparamagnetic iron oxide nanoparticles (PEG-SPIONs) and alternating nonheating magnetic fields. MMA lies in the translation of magnetic forces into mechanical agitation. As a proof of concept, we developed a 2D cell culture model based on human umbilical vein endothelial cells (HUVEC), which were incubated with PEG-SPIONs and then exposed to different magnetic doses. After adjusting the particle concentration, incubation times, and parameters (amplitude, frequency, and exposure time) of the magnetic field generator, we induced actin filament remodeling and subsequent vascular endothelial-cadherin junction disruption. This led to transient gaps in cell monolayers, through which fluorescein isothiocyanate–dextran was translocated. We observed no cell viability reduction for 3 h of particle incubation up to a concentration of 100 μg/mL in the presence and absence of magnetic fields. For optimal permeability studies, the magnetic field parameters were adjusted to 100 mT, 65 Hz, and 30 min in a pulse mode with 5 min OFF intervals. We found that the endothelial permeability reached the highest value (33%) when 2 h postmagnetic field treatment was used. To explain these findings, a magneto-mechanical transduced stress mechanism mediated by intracellular forces was proposed. This method can open new avenues for targeted drug delivery into anatomic regions within the body for a broad range of disease interventions.

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Section: Resultsmentioning

confidence: 43%

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Magneto-Mechanical Actuation Induces Endothelial Permeability

Kanber,

Umerah,

Brindley

et al. 2023

ACS Biomater. Sci. Eng.

View full text Add to dashboard Cite

show abstract

“…The combination of an alternating magnetic field and an external static magnetic field enhanced MNP crossing to ∼63%, compared to ∼50% with just the external static magnetic field alone. Besides, more MNP accumulation in the mouse brain was observed when applying an alternating magnetic field, demonstrating its ability to modulate BBB permeability through the magnetic guidance of NPs . Gkountas et al demonstrated that an EMF could significantly enhance MNP delivery across the BBB.…”

Section: Permeation Mechanisms Of Nanoparticles Capable Of Crossing T...mentioning

confidence: 99%

Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier

Zha,

Liu,

et al. 2024

ACS Nano

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The blood−brain barrier (BBB) is a specialized semipermeable structure that highly regulates exchanges between the central nervous system parenchyma and blood vessels. Thus, the BBB also prevents the passage of various forms of therapeutic agents, nanocarriers, and their cargos. Recently, many multidisciplinary studies focus on developing cargo-loaded nanoparticles (NPs) to overcome these challenges, which are emerging as safe and effective vehicles in neurotheranostics. In this Review, first we introduce the anatomical structure and physiological functions of the BBB. Second, we present the endogenous and exogenous transport mechanisms by which NPs cross the BBB. We report various forms of nanomaterials, carriers, and their cargos, with their detailed BBB uptake and permeability characteristics. Third, we describe the effect of regulating the size, shape, charge, and surface ligands of NPs that affect their BBB permeability, which can be exploited to enhance and promote neurotheranostics. We classify typical functionalized nanomaterials developed for BBB crossing. Fourth, we provide a comprehensive review of the recent progress in developing functional polymeric nanomaterials for applications in multimodal bioimaging, therapeutics, and drug delivery. Finally, we conclude by discussing existing challenges, directions, and future perspectives in employing functionalized nanomaterials for BBB crossing.

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Nanotherapeutics for Alleviating Anesthesia‐Associated Complications

Lu,

Wei,

Shi

et al. 2024

Advanced Science

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Current management of anesthesia‐associated complications falls short in terms of both efficacy and safety. Nanomaterials with versatile properties and unique nano‐bio interactions hold substantial promise as therapeutics for addressing these complications. This review conducts a thorough examination of the existing nanotherapeutics and highlights the strategies for developing prospective nanomedicines to mitigate anesthetics‐related toxicity. Initially, general, regional, and local anesthesia along with the commonly used anesthetics and related prevalent side effects are introduced. Furthermore, employing nanotechnology to prevent and alleviate the complications of anesthetics is systematically demonstrated from three aspects, that is, developing 1) safe nano‐formulization for anesthetics; 2) nano‐antidotes to sequester overdosed anesthetics and alter their pharmacokinetics; 3) nanomedicines with pharmacodynamic activities to treat anesthetics toxicity. Finally, the prospects and challenges facing the clinical translation of nanotherapeutics for anesthesia‐related complications are discussed. This work provides a comprehensive roadmap for developing effective nanotherapeutics to prevent and mitigate anesthesia‐associated toxicity, which can potentially revolutionize the management of anesthesia complications.

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Transmigration of magnetite nanoparticles across the blood–brain barrier in a rodent model: influence of external and alternating magnetic fields

Abstract: Despite advances in neurology, drug delivery to the central nervous system is considered a challenge due to the presence of blood brain barrier (BBB). In this study, the role of...

Cited by 10 publications

References 64 publications

Magneto-Mechanical Actuation Induces Endothelial Permeability

Magneto-Mechanical Actuation Induces Endothelial Permeability

Functionalized Nanomaterials Capable of Crossing the Blood–Brain Barrier

Nanotherapeutics for Alleviating Anesthesia‐Associated Complications

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