Feasibility Study of the Permeability and Uptake of Mesoporous Silica Nanoparticles across the Blood-Brain Barrier

Baghirov, Habib; Karaman, Didem Şen; Viitala, Tapani; Duchanoy, Alain; Lou, Yan-Ru; Mamaeva, Veronika; Pryazhnikov, Evgeny; Khiroug, Leonard; Davies, Catharina de Lange; Sahlgren, Cecilia; Rosenholm, Jessica M.

doi:10.1371/journal.pone.0160705

Cited by 86 publications

(61 citation statements)

References 41 publications

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“…36 Preliminary reports suggest that SiNPs are capable of crossing the blood-brain barrier, making them potentially attractive agents for glioblastoma treatment. [37][38][39][40] Moreover, Ducray et al showed that two sets of modified SiNPs (Si-indocyanine green/polycaprolactonepolylactic acid-rhodamine-doped and indocyanine green/ polycaprolactone-rhodamine-doped NPs) did not impair cell viability or induce neuroinflammation in primary hippocampal cultures. 41 Additionally, animal models have demonstrated the biocompatibility and relative safety of SiNPs for in vivo use in mice and rats.…”

Section: Discussionmentioning

confidence: 99%

Silica nanoparticle-induced oxidative stress and mitochondrial damage is followed by activation of intrinsic apoptosis pathway in glioblastoma cells

Kusaczuk¹,

Krętowski²,

Naumowicz³

et al. 2018

IJN

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IntroductionRecently, the focus of oncological research has been on the optimization of therapeutic strategies targeted at malignant diseases. Nanomedicine utilizing silicon dioxide nanoparticles (SiNPs) is one such strategy and is rapidly developing as a promising tool for cancer diagnosis, imaging, and treatment. Nevertheless, little is known about the mechanisms of action of SiNPs in brain tumors.Materials and methodsHere, we explored the effects of 5–15 nm SiNPs in the human glioblastoma cell line LN229. In this respect, MTT assays, microscopic observations, flow cytometry analyses, and luminescent assays were performed. Moreover, RT-qPCR and Western blot analyses were done to determine gene and protein expressions.ResultsWe demonstrated that SiNPs triggered evident cytotoxicity, with microscopic observations of the nuclei, annexin V–fluorescein isothiocyanate/propidium iodide staining, and elevated caspase 3/7 activity, suggesting that SiNPs predominantly induced apoptotic death in LN229 cells. We further showed the occurrence of oxidative stress induced by enhanced reactive oxygen-species generation. This effect was followed by deregulated expression of genes encoding the antioxidant enzymes SOD1, SOD2, and CAT, and impaired mitochondria function. SiNP- induced mitochondrial dysfunction was characterized by membrane-potential collapse, ATP depletion, elevated expression of BAX, PUMA, and NOXA with simultaneous downregulation of BCL2/BCL2L1, and activation of caspase 9. Moreover, RT-qPCR and Western blot analyses demonstrated increased levels of the endoplasmic reticulum stress markers GRP78, GRP94, and DDIT3, as well as strongly increased expressions of the IL1B and COX2 genes, suggesting activation of endoplasmic reticulum stress and a proinflammatory response.ConclusionsAltogether, our data indicate that in LN229 cells, SiNPs evoke cell death via activation of the intrinsic apoptosis pathway and suggest that other aspects of cellular function may also be affected. As such, SiNPs represent a potentially promising agent for facilitating further progress in brain cancer therapy. However, further exploration of SiNP long-term toxicity and molecular effects is necessary prior to their widespread application.

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Section: Discussionmentioning

confidence: 99%

Silica nanoparticle-induced oxidative stress and mitochondrial damage is followed by activation of intrinsic apoptosis pathway in glioblastoma cells

Kusaczuk¹,

Krętowski²,

Naumowicz³

et al. 2018

IJN

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“…Given the fact, that MSNs have been recognized for their role in delivering therapeutic drugs for various diseases, in the year 2016, Baghirov et al investigated the uptake, transport, and cytotoxicity of MSN based drug nanocarriers functionalized with PEG–PEI block copolymer using in vitro models of the BBB . They used RBE4 rat brain endothelial cells, as well as Madin–Darby canine kidney epithelial cells for their experiments, as given in Figure .…”

Section: Crossing the Blood–brain Barriermentioning

confidence: 99%

“…d) Scanning electron microscopy micrograph of rod‐shaped MSNs. Reproduced under the terms and conditions of the Creative Commons Attribution License . Copyright 2016, Baghirov et al, published by Plos.…”

Section: Crossing the Blood–brain Barriermentioning

confidence: 99%

Multidisciplinary Role of Mesoporous Silica Nanoparticles in Brain Regeneration and Cancers: From Crossing the Blood–Brain Barrier to Treatment

Mendiratta

Hussein

Nasser

et al. 2019

Part & Part Syst Charact

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that by 2040, neurodegenerative diseases will surpass cancer as the second reason of death after cardiovascular diseases in such aged populations. [1,2] As per a 2017 report, neurological diseases cost the United States of America about $800 billion annually and this number is expected to increase even further over the coming years as the percentage of aged citizens increases. [3] Unlike most other major diseases, the pace of drug development and delivery in case of neurodegenerative diseases has been stationary, partially due to lack of biomarkers that can diagnose such diseases long before the neurological symptoms arise and the challenges associated with identification of targets for drugs that can terminate or minimize neurodegeneration. Most importantly, delivering new cerebral therapeutic agents is impeded by the extensive and robust blood-brain barrier (BBB) which prevents the vast majority of drugs from crossing to the brain after systemic administration. During brain infections, intracerebral hemorrhage, or in neurodegenerative disorders, the BBB is altered in such a way that it allows easy access of inflammatory inducing molecules that may cause adverse neuronal damage. [4] Given the importance of early diagnosis and treatment of neurodegenerative diseases, new drug delivery technologies have appeared in the last decade.As shown in Scheme 1, unique nanomaterials have been reported and several nanosized drug delivery systems including liposomes, dendrimers, carbon nanotubes (CNTs), inorganic and hybrid nanoparticles, and polymeric micelles have gained attention and have been tested for targeted drug delivery not only for neurodegenerative diseases but also for several other ailments. [5][6][7][8][9][10] The discovery of MCM-41 was recognized as a major breakthrough in materials science and since then mesoporous silica nanoparticles (MSNs), thanks to their superior physiochemical properties such as large porosity, high surface areas, low toxicity, controllable sizes, and wide range of morphologies compared to conventional nanoparticles (NPs) have emerged as favorable tools in biomedical applications as nanocarriers for encapsulation and delivery of therapeutic medicines. [11][12][13][14] Designing biocompatible MSNs and their multifunctional derivatives for drug transport as well as theranostics is one of the hottest areas of research in the field of nanobiotechnology and nanomedicine. [15][16][17][18][19] High loading capacity, acceptable biocompatibility, and limitless possibilities of surface functionalization for specific cellular recognition Mesoporous silica nanoparticles (MSNs) have gained wide attention for their role in biomedicine and as drug delivery vehicles. Their structural tunability, high surface area, and easy functionalization impart significant advantages over conventional materials. In this Review, recent advances in the synthesis, drug delivery, and therapeutic roles of MSNs in the treatment of various neurodegenerative and neuroinflammatory diseases are presented. The intention is to...

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“…New methods of powder preparation have recently been described for various biomedical applications aiming to control the particle size, the morphological characteristics, as well as encapsulation efficiency [ 28 , 29 , 30 ]. The association of drugs with micro- and nanoparticle carrier systems has allowed to overcome the challenges in the development of inhaled therapeutic systems [ 27 , 31 , 32 , 33 ], and to modulate the drug release profiles [ 34 , 35 ]. Another important point to consider is the ability of the particles to circunvent the mechanisms of defense of the lung against foreign substances, besides being non-toxic and biocompatible (20).…”

Section: Introductionmentioning

confidence: 99%

An Inhalable Powder Formulation Based on Micro- and Nanoparticles Containing 5-Fluorouracil for the Treatment of Metastatic Melanoma

Zatta

Frank

Reolon³

et al. 2018

Nanomaterials

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Melanoma is the most aggressive and lethal type of skin cancer, with a poor prognosis because of the potential for metastatic spread. The aim was to develop innovative powder formulations for the treatment of metastatic melanoma based on micro- and nanocarriers containing 5-fluorouracil (5FU) for pulmonary administration, aiming at local and systemic action. Therefore, two innovative inhalable powder formulations were produced by spray-drying using chondroitin sulfate as a structuring polymer: (a) 5FU nanoparticles obtained by piezoelectric atomization (5FU-NS) and (b) 5FU microparticles of the mucoadhesive agent Methocel™ F4M for sustained release produced by conventional spray drying (5FU-MS). The physicochemical and aerodynamic were evaluated in vitro for both systems, proving to be attractive for pulmonary delivery. The theoretical aerodynamic diameters obtained were 0.322 ± 0.07 µm (5FU-NS) and 1.138 ± 0.54 µm (5FU-MS). The fraction of respirable particles (FR%) were 76.84 ± 0.07% (5FU-NS) and 55.01 ± 2.91% (5FU-MS). The in vitro mucoadhesive properties exhibited significant adhesion efficiency in the presence of Methocel™ F4M. 5FU-MS and 5FU-NS were tested for their cytotoxic action on melanoma cancer cells (A2058 and A375) and both showed a cytotoxic effect similar to 5FU pure at concentrations of 4.3 and 1.7-fold lower, respectively.

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Feasibility Study of the Permeability and Uptake of Mesoporous Silica Nanoparticles across the Blood-Brain Barrier

Cited by 86 publications

References 41 publications

Silica nanoparticle-induced oxidative stress and mitochondrial damage is followed by activation of intrinsic apoptosis pathway in glioblastoma cells

Silica nanoparticle-induced oxidative stress and mitochondrial damage is followed by activation of intrinsic apoptosis pathway in glioblastoma cells

Multidisciplinary Role of Mesoporous Silica Nanoparticles in Brain Regeneration and Cancers: From Crossing the Blood–Brain Barrier to Treatment

An Inhalable Powder Formulation Based on Micro- and Nanoparticles Containing 5-Fluorouracil for the Treatment of Metastatic Melanoma

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