Localization and Mobility of glucose-coated Gold Nanoparticles Within the Brain

Gromnicova, Radka; Yılmaz, Canan Uğur; Orhan, Nurcan; Kaya, Mehmet; Davies, Heather A.; Williams, Philip M.; Romero, Ignacio A.; Sharrack, Basil; Male, David

doi:10.2217/nnm.15.215

Cited by 35 publications

(31 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The work of our group has shown that gold nanoparticles rapidly cross brain endothelium in vitro and in vivo [13,22]. Here, we have replaced some of the galactose ligand on the nanoparticles with oligonucleotides to model a therapeutic cargo.…”

Section: Discussionmentioning

confidence: 99%

“…A variety of nanoparticles have been used to transport therapeutic agents across the blood-brain barrier [9], including gold nanoparticles [10,11]. Previously, we have shown that small gold nanoparticles (2nm) are able to rapidly cross brain endothelium in vitro and in vivo and enter astrocytes or other cells of the brain [12,13]. The small size of these nanoparticles means that they 5 are able to cross brain endothelium by vesicular transcytosis or by direct movement across the apical and basal plasma membranes via the cytosol [14].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Gold nanocarriers for transport of oligonucleotides across brain endothelial cells

Fatima

Gromnicova

Loughlin

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Treatment of diseases that affect the CNS by gene therapy requires delivery of oligonucleotides to target cells within the brain. As the blood brain barrier prevents movement of large biomolecules, current approaches involve direct injection of the oligonucleotides, which is invasive and may have only a localised effect. The aim of this study was to investigate the potential of 2 nm galactose-coated gold nanoparticles (NP-Gal) as a delivery system of oligonucleotides across brain endothelium.DNA oligonucleotides of different types were attached to NP-Gal by the place exchange reaction and were characterised by EMSA (electrophoretic mobility shift assay). Several nanoparticle formulations were created, with single-or double-stranded (20nt or 40nt) DNA oligonucleotides, or with different amounts of DNA attached to the carriers. These nanocarriers were applied to transwell cultures of human brain endothelium in vitro (hCMEC/D3 cell-line) or to a 3D-hydrogel model of the blood-brain barrier including astrocytes. Transfer rates were measured by quantitative electron microscopy for the nanoparticles and qPCR for DNA.Despite the increase in nanoparticle size caused by attachment of oligonucleotides to the NP-Gal carrier, the rates of endocytosis and transcytosis of nanoparticles were both considerably increased when they carried an oligonucleotide cargo. Carriers with 40nt dsDNA were most efficient, accumulating in vesicles, in the cytosol and beneath the basal membrane of the endothelium. The oligonucleotide cargo remained attached to the nanocarriers during transcytosis and the transport rate across the endothelial cells was increased at least 50fold compared with free DNA. The nanoparticles entered the extracellular matrix and were taken up by the astrocytes in biologically functional amounts.Attachment of DNA confers a strong negative charge to the nanoparticles which may explain the enhanced binding to the endothelium and transcytosis by both vesicular transport and the transmembrane/cytosol pathway. These gold nanoparticles have the potential to transport therapeutic amounts of nucleic acids into the CNS.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gold nanocarriers for transport of oligonucleotides across brain endothelial cells

Fatima

Gromnicova

Loughlin

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Of note, nanoparticles that are coated with hydrophilic shell manufactured by long polymer chains with high fructose density have great affinity to tumor cells [14]. Since biocompatibility, relative non-toxic property and the capability to cross the blood-brain barrier, GCNs are widely used as the radiosensitizer in radiotherapy and can carry therapeutic biomolecules into brain [44,45].…”

Section: Discussionmentioning

confidence: 99%

Sialic acid-binding lectin-modified fructose-coated nanoparticles: a promising targeted therapeutic synthetic for breast cancers

Zhang

Song

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Sialic acid-binding lectin (cSBL) specifically kills tumor cells rather than healthy cells. Glycopolymer-coated nanoparticles are selectively ingested by tumor cells because they can interact with the enriched carbohydrate receptors located on the surface of tumor cells. In this context, we synthesized cSBL-modified fructose-coated nanoparticles (LMFN) and cSBL-modified glucose-coated nanoparticles (LMGN) to investigate their anticancer activity in various molecular subtypes of breast cancer cell lines. Methods: The syntheses of fructose-coated nanoparticles and glucose-coated nanoparticles were based on the chemicals of 1,2:4,5-di- O -isopropylidene- β -d-fructopyranose and 1,2:4,5-di- O -isopropylidene- β -d-glucopyranose, respectively. The carbodiimide-based method was employed to synthesize LMFN and LMGN. The antitumor mechanism was explored by cell cycle analysis with flowcytometry and the antitumor activity was assessed by cytotoxicity assay and multiple drug effects analysis. Results: The cytotoxicity assay showed that LMFN had robust antitumor activity against all breast cancer phenotype cell lines whereas LMGN was rarely efficacious to against human epidermal growth factor receptor 2-positive/overexpression (HER2+/overexpression) breast cancer cells. The intrinsic reason for these findings was that the overexpression of fructose transporter, GLUT5, was observed in all breast cancer subtype cell lines but only a paucity of glucose transporter, GLUT1, was expressed in HER2+/overexpression breast cancer cell lines that dampened the uptake of LMGN to these cells. The cell cycle analysis indicated that the anticancer activity of LMFN was achieved by arresting cell cycle in S phase. The multiple drug effects analysis suggested the synergistic effect in the combinations of LMFN and tamoxifen to kill estrogen receptor+ breast cancer cells and LMFN and trastuzumab to kill HER2+/overexpressed breast cancer cells. Conclusion: Our work pinpoints that LMFN may be a new-onset selection for molecularly targeted therapy of breast cancers and paves the way for establishing its clinical application in the future.

show abstract

“…Gold nanoparticles were chosen as a proof-of-concept and for their general relevance in nanomedicine [15]. Recent examples that make use of biomolecules conjugated to gold nanoparticles include delivery of Cas9 ribonucleoprotein and donor DNA for in vivo genome editing [16] and drug delivery across the blood-brain barrier [17].…”

Section: Modular Assembly Of Proteins On Gold Nanoparticlesmentioning

confidence: 99%

A Plug and Play Approach for the Decoration of Nanoparticles With Recombinant Proteins

Ferrari

2018

Nanomedicine (Lond.)

View full text Add to dashboard Cite

show abstract

Localization and Mobility of glucose-coated Gold Nanoparticles Within the Brain

Cited by 35 publications

References 27 publications

Gold nanocarriers for transport of oligonucleotides across brain endothelial cells

Gold nanocarriers for transport of oligonucleotides across brain endothelial cells

Sialic acid-binding lectin-modified fructose-coated nanoparticles: a promising targeted therapeutic synthetic for breast cancers

A Plug and Play Approach for the Decoration of Nanoparticles With Recombinant Proteins

Contact Info

Product

Resources

About