Quantification of blood–brain barrier transport and neuronal toxicity of unlabelled multiwalled carbon nanotubes as a function of surface charge

Gonzalez‐Carter, Daniel; Goode, Angela E.; Kiryushko, Darya; Masuda, Seigo; Hu, Sheng; Rodrigues, Rosália Lopes; Dexter, David T.; Shaffer, Milo S. P.; Porter, Alexandra E.

doi:10.1039/c9nr02866h

Cited by 36 publications

(24 citation statements)

References 62 publications

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“…C-BNM are known to induce either physical or biological damage to the cell membrane, membranes of organelles along with destabilization of actin filaments, the cytoskeleton and effecting the cell cycle [44][45][46]. At the tissue and cellular levels, the mechanisms responsible for inflammation are based on disruption of various barriers (e.g., alveolar-capillary barrier, blood-brain barrier), infiltration of immune cells and their interaction with molecules released from injured cells (disease associated molecular patterns) or with nanoparticles themselves [47]. A recent study demonstrating destabilisation of phospholipid membranes by carbon nanosheets was published recently by [48].…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory Effect of Carbon-Based Nanomaterials: In Vitro Study on Stimulation of Inflammasome NLRP3 via Destabilisation of Lysosomes

et al. 2020

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Carbon-based nanomaterials (C-BNM) have recently attracted an increased attention as the materials with potential applications in industry and medicine. Bioresistance and proinflammatory potential of C-BNM is the main obstacle for their medicinal application which was documented in vivo and in vitro. However, there are still limited data especially on graphene derivatives such as graphene platelets (GP). In this work, we compared multi-walled carbon nanotubes (MWCNT) and two different types of pristine GP in their potential to activate inflammasome NLRP3 (The nod-like receptor family pyrin domain containing 3) in vitro. Our study is focused on exposure of THP-1/THP1-null cells and peripheral blood monocytes to C-BNM as representative models of canonical and alternative pathways, respectively. Although all nanomaterials were extensively accumulated in the cytoplasm, increasing doses of all C-BNM did not lead to cell death. We observed direct activation of NLRP3 via destabilization of lysosomes and release of cathepsin B into cytoplasm only in the case of MWCNTs. Direct activation of NLRP3 by both GP was statistically insignificant but could be induced by synergic action with muramyl dipeptide (MDP), as a representative molecule of the family of pathogen-associated molecular patterns (PAMPs). This study demonstrates a possible proinflammatory potential of GP and MWCNT acting through NLRP3 activation.

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Section: Discussionmentioning

confidence: 99%

Proinflammatory Effect of Carbon-Based Nanomaterials: In Vitro Study on Stimulation of Inflammasome NLRP3 via Destabilisation of Lysosomes

et al. 2020

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“…Leeper's group has recently used PEG-functionalized SWNTs loaded with a fluorescent probe and a small-molecule inhibitor of the anti-phagocytic CD47-SIRPα signaling axis in order to prevent atherosclerosis [39]. Being capable of easily penetrating the cells, CNTs hold certain potential of crossing the blood-brain barrier (BBB) to treat neurological diseases [40]. Porter's group found that functionalized anionic MWNTs have the highest transportation rate across the human BBB [40].…”

Section: Carbon Nanotubesmentioning

confidence: 99%

“…Being capable of easily penetrating the cells, CNTs hold certain potential of crossing the blood-brain barrier (BBB) to treat neurological diseases [40]. Porter's group found that functionalized anionic MWNTs have the highest transportation rate across the human BBB [40].…”

Section: Carbon Nanotubesmentioning

confidence: 99%

“…In terms of the safety profile of the CNTs, studies suggested that endocytosis of the CNTs induces oxidative stress to the cells, revealing a close connection between CNTs and inflammation, fibrosis, and cancer, impeding the translational value of this nanocarrier [41,42]. In addition, the toxicity of CNTs is not only related to their shape but also to their surface charge [40,[43][44][45][46].…”

Section: Carbon Nanotubesmentioning

confidence: 99%

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Recent Advances in Nanocarrier-Assisted Therapeutics Delivery Systems

Kang

2020

Pharmaceutics

150

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Nanotechnologies have attracted increasing attention in their application in medicine, especially in the development of new drug delivery systems. With the help of nano-sized carriers, drugs can reach specific diseased areas, prolonging therapeutic efficacy while decreasing undesired side-effects. In addition, recent nanotechnological advances, such as surface stabilization and stimuli-responsive functionalization have also significantly improved the targeting capacity and therapeutic efficacy of the nanocarrier assisted drug delivery system. In this review, we evaluate recent advances in the development of different nanocarriers and their applications in therapeutics delivery.

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“…Once sufficiently confluent (~70%), adherent cells were detached from the surface of the flasks using trypsin and the cells were seeded at 300,000 cells/cm 2 into the 3.0 µm pore polycarbonate membrane inserts of 6-and 96-well Costar Transwell ® plates precoated with 1:20 type 1 collagen from calf skin: DPBS (1 h) and 1:100 fibronectin from bovine plasma: DPBS (1 h). The hCMEC/D3 cells were exposed to VEGF-free media for 72 h prior to testing to promote tight junction formation [48,50,52,53].…”

Section: Hcmec/d3 Cell Culturementioning

confidence: 99%

Micellar Nanocarriers of Hydroxytyrosol Are Protective against Parkinson’s Related Oxidative Stress in an In Vitro hCMEC/D3-SH-SY5Y Co-Culture System

Mursaleen

Noble

Somavarapu³

et al. 2021

Antioxidants

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Hydroxytyrosol (HT) is a natural phenolic antioxidant which has neuroprotective effects in models of Parkinson’s disease (PD). Due to issues such as rapid metabolism, HT is unlikely to reach the brain at therapeutic concentrations required for a clinical effect. We have previously developed micellar nanocarriers from Pluronic F68® (P68) and dequalinium (DQA) which have suitable characteristics for brain delivery of antioxidants and iron chelators. The aim of this study was to utilise the P68 + DQA nanocarriers for HT alone, or in combination with the iron chelator deferoxamine (DFO), and assess their physical characteristics and ability to pass the blood–brain barrier and protect against rotenone in a cellular hCMEC/D3-SH-SY5Y co-culture system. Both HT and HT + DFO formulations were less than 170 nm in size and demonstrated high encapsulation efficiencies (up to 97%). P68 + DQA nanoformulation enhanced the mean blood–brain barrier (BBB) passage of HT by 50% (p < 0.0001, n = 6). This resulted in increased protection against rotenone induced cytotoxicity and oxidative stress by up to 12% and 9%, respectively, compared to the corresponding free drug treatments (p < 0.01, n = 6). This study demonstrates for the first time the incorporation of HT and HT + DFO into P68 + DQA nanocarriers and successful delivery of these nanocarriers across a BBB model to protect against PD-related oxidative stress. These nanocarriers warrant further investigation to evaluate whether this enhanced neuroprotection is exhibited in in vivo PD models.

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Quantification of blood–brain barrier transport and neuronal toxicity of unlabelled multiwalled carbon nanotubes as a function of surface charge

Abstract: Directly and accurately characterizing the transport of nanoparticles across the blood–brain barrier will greatly advance the delivery of therapies against brain disorders.

Cited by 36 publications

References 62 publications

Proinflammatory Effect of Carbon-Based Nanomaterials: In Vitro Study on Stimulation of Inflammasome NLRP3 via Destabilisation of Lysosomes

Proinflammatory Effect of Carbon-Based Nanomaterials: In Vitro Study on Stimulation of Inflammasome NLRP3 via Destabilisation of Lysosomes

Recent Advances in Nanocarrier-Assisted Therapeutics Delivery Systems

Micellar Nanocarriers of Hydroxytyrosol Are Protective against Parkinson’s Related Oxidative Stress in an In Vitro hCMEC/D3-SH-SY5Y Co-Culture System

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