Magnetic Nanoparticles in the Central Nervous System: Targeting Principles, Applications and Safety Issues

D’Agata, Federico; Ruffinatti, Federico Alessandro; Boschi, Silvia; Stura, Ilaria; Rainero, Innocenzo; Abollino, Ornella; Cavalli, Roberta; Guiot, Caterina

doi:10.3390/molecules23010009

Cited by 70 publications

(68 citation statements)

References 94 publications

(255 reference statements)

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“…Different inorganic nanoparticular carriers have been applied in this field, e.g. iron oxide, cerium oxide, molybdenum, silica or gold nanoparticles [40][41][42][43][44] . Compared to other types of nanoparticles, gold nanoparticles have received considerable www.nature.com/scientificreports/ interest because of their relative low cytotoxicity, predominant optical properties for imaging, well-established syntheses, and their potential to cross the BBB 14,28,45,46 .…”

Section: Discussionmentioning

confidence: 99%

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Transport of ultrasmall gold nanoparticles (2 nm) across the blood–brain barrier in a six-cell brain spheroid model

Sokolova

Mekky

Meer

et al. 2020

Sci Rep

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The blood–brain barrier (BBB) is an efficient barrier for molecules and drugs. Multicellular 3D spheroids display reproducible BBB features and functions. The spheroids used here were composed of six brain cell types: Astrocytes, pericytes, endothelial cells, microglia cells, oligodendrocytes, and neurons. They form an in vitro BBB that regulates the transport of compounds into the spheroid. The penetration of fluorescent ultrasmall gold nanoparticles (core diameter 2 nm; hydrodynamic diameter 3–4 nm) across the BBB was studied as a function of time by confocal laser scanning microscopy, with the dissolved fluorescent dye (FAM-alkyne) as a control. The nanoparticles readily entered the interior of the spheroid, whereas the dissolved dye alone did not penetrate the BBB. We present a model that is based on a time-dependent opening of the BBB for nanoparticles, followed by a rapid diffusion into the center of the spheroid. After the spheroids underwent hypoxia (0.1% O2; 24 h), the BBB was more permeable, permitting the uptake of more nanoparticles and also of dissolved dye molecules. Together with our previous observations that such nanoparticles can easily enter cells and even the cell nucleus, these data provide evidence that ultrasmall nanoparticle can cross the blood brain barrier.

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Section: Discussionmentioning

confidence: 99%

“…It was shown that 2 h after injection, 20 nm gold nanoparticles had a broad biodistribution and a considerable accumulation within the brain. The possibility to apply steady and alternating magnetic fields to drive magnetic nanoparticles and liposomes across the BBB was also shown 21,40,51 .…”

Section: Discussionmentioning

confidence: 99%

Transport of ultrasmall gold nanoparticles (2 nm) across the blood–brain barrier in a six-cell brain spheroid model

Sokolova

Mekky

Meer

et al. 2020

Sci Rep

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“…With combined fluorophore, the position of MNPs could be directly tracked in the brain parenchyma of normal mice, which also allow cellular-level by confocal microscopy. The magnetic nanoparticles could target for extravasation and assembly by apply magnetic field which could be used for crossing BBB drug delivery to treatment of various CNS diseases [ 100 , 101 , 102 ].…”

Section: Research Progress In Methods For Blood–brain Barrier Permmentioning

confidence: 99%

Towards Improvements for Penetrating the Blood–Brain Barrier—Recent Progress from a Material and Pharmaceutical Perspective

Liu

Liang

et al. 2018

Cells

238

129

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The blood–brain barrier (BBB) is a critical biological structure that prevents damage to the brain and maintains its bathing microenvironment. However, this barrier is also the obstacle to deliver beneficial drugs to treat CNS (central nervous system) diseases. Many efforts have been made for improvement of delivering drugs across the BBB in recent years to treat CNS diseases. In this review, the anatomical and functional structure of the BBB is comprehensively discussed. The mechanisms of BBB penetration are summarized, and the methods and effects on increasing BBB permeability are investigated in detail. It also elaborates on the physical, chemical, biological and nanocarrier aspects to improve drug delivery penetration to the brain and introduces some specific drug delivery effects on BBB permeability.

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“…However, very few studies have been performed using AgNPs as drug delivery systems as a treatment of CNS neurons, especially due to several safety-related aspects [29][30][31]. But these safety issues are not only associated with AgNPs; in fact, in spite of all of the mentioned advantageous properties of inorganic NPs, the majority still have major drawbacks and have been shown to be particularly critical for the brain, as they can induce neurotoxicity, neuroinflammation and can permanently alter the BBB permeability [23,32,33].…”

Section: Inorganic Nanosystemsmentioning

confidence: 99%

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

et al. 2020

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Central nervous system (CNS) disorders encompass a vast spectrum of pathological conditions and represent a growing concern worldwide. Despite the high social and clinical interest in trying to solve these pathologies, there are many challenges to bridge in order to achieve an effective therapy. One of the main obstacles to advancements in this field that has hampered many of the therapeutic strategies proposed to date is the presence of the CNS barriers that restrict the access to the brain. However, adequate brain biodistribution and neuronal cells specific accumulation in the targeted site also represent major hurdles to the attainment of a successful CNS treatment. Over the last few years, nanotechnology has taken a step forward towards the development of therapeutics in neurologic diseases and different approaches have been developed to surpass these obstacles. The versatility of the designed nanocarriers in terms of physical and chemical properties, and the possibility to functionalize them with specific moieties, have resulted in improved neurotargeted delivery profiles. With the concomitant progress in biology research, many of these strategies have been inspired by nature and have taken advantage of physiological processes to achieve brain delivery. Here, the different nanosystems and targeting moieties used to achieve a neuronal delivery reported in the open literature are comprehensively reviewed and critically discussed, with emphasis on the most recent bioinspired advances in the field. Finally, we express our view on the paramount challenges in targeted neuronal delivery that need to be overcome for these promising therapeutics to move from the bench to the bedside.

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Magnetic Nanoparticles in the Central Nervous System: Targeting Principles, Applications and Safety Issues

Cited by 70 publications

References 94 publications

Transport of ultrasmall gold nanoparticles (2 nm) across the blood–brain barrier in a six-cell brain spheroid model

Transport of ultrasmall gold nanoparticles (2 nm) across the blood–brain barrier in a six-cell brain spheroid model

Towards Improvements for Penetrating the Blood–Brain Barrier—Recent Progress from a Material and Pharmaceutical Perspective

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

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