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  1. Article ; Online: Cellular uptake of nanoparticles

    Tore Skotland / Tore Geir Iversen / Kirsten Sandvig

    Precision Nanomedicine (2021)

    Involvement of caveolae?

    2021  

    Abstract: We here discuss shortly some pitfalls and challenges when investigating which endocytic mechanisms that are involved in cellular uptake of nanoparticles. We specifically discuss some common misunderstandings regarding studies claimed to demonstrate ... ...

    Abstract We here discuss shortly some pitfalls and challenges when investigating which endocytic mechanisms that are involved in cellular uptake of nanoparticles. We specifically discuss some common misunderstandings regarding studies claimed to demonstrate uptake via caveolae. Scientists in the nanomedicine field should be aware of that reduction in the membrane content of cholesterol by adding methyl-β-cyclodextrin not only removes caveolae, but inhibits other uptake mechanisms, such as macropinocytosis, as well. Furthermore, the general tyrosine kinase inhibitor genistein is not a specific inhibitor of uptake from caveolae. Moreover, one can still see that scientists in the field write that they want to direct transport of their particles to caveolae and caveosomes to avoid lysosomal degradation. However, caveosomes are artefacts caused by overexpression of caveolin-1 constructs, and ligands or particles taken up by caveolae are transported to endosomes and lysosomes as reported for other types of endocytosis.
    Keywords Medicine ; R ; Medical technology ; R855-855.5
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Andover House Inc.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Modulation of Ricin Intoxication by the Autophagy Inhibitor EACC

    Kirsten Sandvig / Simona Kavaliauskiene / Anne Grethe Myrann / Tore Geir Iversen / Tore Skotland

    Toxins, Vol 14, Iss 360, p

    2022  Volume 360

    Abstract: The compound EACC (ethyl (2-(5-nitrothiophene-2-carboxamido) thiophene-3-carbonyl) carbamate) was recently reported to inhibit fusion of autophagosomes with lysosomes in a reversible manner by inhibiting recruitment of syntaxin 17 to autophagosomes. We ... ...

    Abstract The compound EACC (ethyl (2-(5-nitrothiophene-2-carboxamido) thiophene-3-carbonyl) carbamate) was recently reported to inhibit fusion of autophagosomes with lysosomes in a reversible manner by inhibiting recruitment of syntaxin 17 to autophagosomes. We report here that this compound also provides a strong protection against the protein toxin ricin as well as against other plant toxins such as abrin and modeccin. The protection did not seem to be caused by inhibition of endocytosis and retrograde transport, but rather by inhibited release of the enzymatically active A-moiety to the cytosol. The TANK-binding kinase 1 (TBK1) has been reported to phosphorylate syntaxin 17 and be required for initiation of autophagy. The inhibitor of TBK1, MRT68601, induced in itself a strong sensitization to ricin, apparently by increasing transport to the Golgi apparatus. Importantly, MRT68601 increased Golgi transport of ricin even in the presence of EACC, but EACC was still able to inhibit intoxication, supporting the idea that EACC protects at a late step along the retrograde pathway. These results also indicate that phosphorylation of syntaxin 17 is not required for the protection observed.
    Keywords ricin ; abrin ; volkensin ; viscumin ; modeccin ; plant toxins ; Medicine ; R
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Cell-Penetrating Peptides

    Tore Skotland / Tore Geir Iversen / Maria Lyngaas Torgersen / Kirsten Sandvig

    Molecules, Vol 20, Iss 7, Pp 13313-

    Possibilities and Challenges for Drug Delivery in Vitro and in Vivo

    2015  Volume 13323

    Abstract: In this review, we discuss how cell-penetrating peptides (CPPs) might get access to their intracellular targets. We specifically focus on the challenge of deciding whether the positively-charged CPPs are just bound to the negatively-charged cell surface ... ...

    Abstract In this review, we discuss how cell-penetrating peptides (CPPs) might get access to their intracellular targets. We specifically focus on the challenge of deciding whether the positively-charged CPPs are just bound to the negatively-charged cell surface and subsequently endocytosed or actually transported into the cytosol, either by direct plasma membrane penetration or after endocytosis. This discussion includes comments about pitfalls when using pharmacological inhibitors in such studies. The possibility of exploiting CPPs as carriers for the delivery of drugs of different sizes in vitro is discussed, as is the use of CPPs as carriers for therapeutic drugs or contrast agents in vivo. We conclude that in many cases, more studies are needed to demonstrate conclusively whether increased delivery of a substance attached to CPPs is due to a membrane-penetrating property or whether the increase is a consequence of just changing the charge of the substance to be delivered. Finally, the expected dose needed for the use of such conjugates in vivo is discussed, including aspects to consider in order to bring potential products into clinical use.
    Keywords cell-penetrating peptides ; cellular uptake ; endocytosis ; drug delivery ; in vivo dose ; pharmaceutical development ; Organic chemistry ; QD241-441
    Subject code 610
    Language English
    Publishing date 2015-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Biodistribution of Poly(alkyl cyanoacrylate) Nanoparticles in Mice and Effect on Tumor Infiltration of Macrophages into a Patient-Derived Breast Cancer Xenograft

    Abhilash D. Pandya / Tore-Geir Iversen / Siver Moestue / Maria T. Grinde / Ýrr Mørch / Sofie Snipstad / Andreas K. O. Åslund / Geir F. Øy / Wanja Kildal / Olav Engebråten / Kirsten Sandvig / Tore Skotland / Gunhild M. Mælandsmo

    Nanomaterials, Vol 11, Iss 1140, p

    2021  Volume 1140

    Abstract: We have investigated the biodistribution and tumor macrophage infiltration after intravenous injection of the poly(alkyl cyanoacrylate) nanoparticles (NPs): PEBCA (poly(2-ethyl-butyl cyanoacrylate), PBCA (poly(n-butyl cyanoacrylate), and POCA (poly(octyl ...

    Abstract We have investigated the biodistribution and tumor macrophage infiltration after intravenous injection of the poly(alkyl cyanoacrylate) nanoparticles (NPs): PEBCA (poly(2-ethyl-butyl cyanoacrylate), PBCA (poly(n-butyl cyanoacrylate), and POCA (poly(octyl cyanoacrylate), in mice. These NPs are structurally similar, have similar PEGylation, and have previously been shown to give large variations in cellular responses in vitro. The PEBCA NPs had the highest uptake both in the patient-derived breast cancer xenograft MAS98.12 and in lymph nodes, and therefore, they are the most promising of these NPs for delivery of cancer drugs. High-resolution magic angle spinning magnetic resonance (HR MAS MR) spectroscopy did not reveal any differences in the metabolic profiles of tumors following injection of the NPs, but the PEBCA NPs resulted in higher tumor infiltration of the anti-tumorigenic M1 macrophages than obtained with the two other NPs. The PEBCA NPs also increased the ratio of M1/M2 (anti-tumorigenic/pro-tumorigenic) macrophages in the tumors, suggesting that these NPs might be used both as a vehicle for drug delivery and to modulate the immune response in favor of enhanced therapeutic effects.
    Keywords poly(alkyl cyanoacrylate) nanoparticles ; breast cancer ; biodistribution ; macrophage infiltration ; magnetic resonance spectroscopy ; Chemistry ; QD1-999
    Subject code 500
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: The alkyl side chain of PACA nanoparticles dictates the impact on cellular stress responses and the mode of particle-induced cell death

    Marzena Szwed / Tonje Sønstevold / Anders Øverbye / Nikolai Engedal / Beata Grallert / Ýrr A Mørch / Tore-Geir Iversen / Tore Skotland / Kirsten Sandvig / Maria L Torgersen

    Abstract: AbstractFor optimal exploitation of nanoparticles (NPs) in biomedicine, and to predict nanotoxicity, detailed knowledge on the cellular responses to cell-bound or internalized NPs is imperative. The outcome of NP-cell interaction is dictated by the type ... ...

    Abstract AbstractFor optimal exploitation of nanoparticles (NPs) in biomedicine, and to predict nanotoxicity, detailed knowledge on the cellular responses to cell-bound or internalized NPs is imperative. The outcome of NP-cell interaction is dictated by the type and magnitude of the NP insult and the cellular response. Here, we have systematically studied the impact of minor differences in NP composition on cellular stress responses and viability by using highly similar poly(alkylcyanoacrylate) (PACA) particles. Surprisingly, PACA particles differing only in their alkyl side chains; butyl (PBCA), ethylbutyl (PEBCA), or octyl (POCA), respectively, induced different stress responses and modes of cell death in human cell lines. POCA particles induced endoplasmic reticulum stress and apoptosis. In contrast, PBCA and PEBCA particles induced lipid peroxidation by depletion of the main cellular antioxidant glutathione (GSH), in a manner depending on the levels of the GSH precursor cystine, and transcription of the cystine transporter SLC7A11 regulated by ATF4 and Nrf2. Intriguingly, these particles activated the recently discovered cell death mechanism ferroptosis, which constitutes a promising alternative for targeting multidrug-resistant cancer stem-like cells. Of the two, PBCA was the strongest inducer. In summary, our findings highlight the cellular sensitivity to nanoparticle composition and have important implications for the choice of PACA monomer in therapeutical settings.
    Keywords covid19
    Publisher biorxiv
    Document type Article ; Online
    DOI 10.1101/304618
    Database COVID19

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  6. Article: Cabazitaxel-loaded Poly(2-ethylbutyl cyanoacrylate) nanoparticles improve treatment efficacy in a patient derived breast cancer xenograft

    Fusser, Markus / Abhilash D. Pandya / Anders Øverbye / Einar Sulheim / Gunhild M. Mælandsmo / Hanne Arenberg Askautrud / Karianne Giller Fleten / Kirsten Sandvig / Kjersti Flatmark / Olav Engebraaten / Sofie Snipstad / Sven Even Borgos / Tore Geir Iversen / Tore Skotland / Wanja Kildal / Ýrr Mørch

    Journal of controlled release. 2019 Jan. 10, v. 293

    2019  

    Abstract: The effect of poly(2-ethyl-butyl cyanoacrylate) nanoparticles containing the cytotoxic drug cabazitaxel was studied in three breast cancer cell lines and one basal-like patient-derived xenograft model grown in the mammary fat pad of immunodeficient mice. ...

    Abstract The effect of poly(2-ethyl-butyl cyanoacrylate) nanoparticles containing the cytotoxic drug cabazitaxel was studied in three breast cancer cell lines and one basal-like patient-derived xenograft model grown in the mammary fat pad of immunodeficient mice. Nanoparticle-encapsulated cabazitaxel had a much better efficacy than similar concentrations of free drug in the basal-like patient-derived xenograft and resulted in complete remission of 6 out of 8 tumors, whereas free drug gave complete remission only with 2 out of 9 tumors. To investigate the different efficacies obtained with nanoparticle-encapsulated versus free cabazitaxel, mass spectrometry quantification of cabazitaxel was performed in mice plasma and selected tissue samples. Nanoparticle-encapsulated drug had a longer circulation time in blood. There was approximately a three times higher drug concentration in tumor tissue 24 h after injection, and two times higher 96 h after injection of nanoparticles with drug compared to the free drug. The tissue biodistribution obtained after 24 h using mass spectrometry analyses correlates well with biodistribution data obtained using IVIS® Spectrum in vivo imaging of nanoparticles labeled with the fluorescent substance NR668, indicating that these data also are representative for the nanoparticle distribution. Furthermore, immunohistochemistry was used to estimate infiltration of macrophages into the tumor tissue following injection of nanoparticle-encapsulated and free cabazitaxel. The higher infiltration of anti-tumorigenic versus pro-tumorigenic macrophages in tumors treated with the nanoparticles might also contribute to the improved effect obtained with the nanoparticle-encapsulated drug. Tumor infiltration of pro-tumorigenic macrophages was four times lower when using nanoparticles containing cabazitaxel than when using particles without drug, and we speculate that the very good therapeutic efficacy obtained with our cabazitaxel-containing particles may be due to their ability to reduce the level of pro-tumorigenic macrophages in the tumor. In summary, encapsulation of cabazitaxel in poly(2-ethyl-butyl cyanoacrylate) nanoparticles seems promising for treatment of breast cancer.
    Keywords blood ; breast neoplasms ; cell lines ; cytotoxicity ; drugs ; encapsulation ; fluorescent substances ; image analysis ; immunohistochemistry ; macrophages ; mass spectrometry ; mice ; models ; nanoparticles ; neoplasm cells ; patients ; remission ; therapeutics
    Language English
    Dates of publication 2019-0110
    Size p. 183-192.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 632533-6
    ISSN 1873-4995 ; 0168-3659
    ISSN (online) 1873-4995
    ISSN 0168-3659
    DOI 10.1016/j.jconrel.2018.11.029
    Database NAL-Catalogue (AGRICOLA)

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    Zs.A 2055: Show issues Location:
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  7. Article ; Online: Cytotoxicity of Poly(Alkyl Cyanoacrylate) Nanoparticles

    Einar Sulheim / Tore-Geir Iversen / Vu To Nakstad / Geir Klinkenberg / Håvard Sletta / Ruth Schmid / Anne Rein Hatletveit / Ane Marit Wågbø / Anders Sundan / Tore Skotland / Kirsten Sandvig / Ýrr Mørch

    International Journal of Molecular Sciences, Vol 18, Iss 11, p

    2017  Volume 2454

    Abstract: Although nanotoxicology has become a large research field, assessment of cytotoxicity is often reduced to analysis of one cell line only. Cytotoxicity of nanoparticles is complex and should, preferentially, be evaluated in several cell lines with ... ...

    Abstract Although nanotoxicology has become a large research field, assessment of cytotoxicity is often reduced to analysis of one cell line only. Cytotoxicity of nanoparticles is complex and should, preferentially, be evaluated in several cell lines with different methods and on multiple nanoparticle batches. Here we report the toxicity of poly(alkyl cyanoacrylate) nanoparticles in 12 different cell lines after synthesizing and analyzing 19 different nanoparticle batches and report that large variations were obtained when using different cell lines or various toxicity assays. Surprisingly, we found that nanoparticles with intermediate degradation rates were less toxic than particles that were degraded faster or more slowly in a cell-free system. The toxicity did not vary significantly with either the three different combinations of polyethylene glycol surfactants or with particle size (range 100–200 nm). No acute pro- or anti-inflammatory activity on cells in whole blood was observed.
    Keywords nanoparticles ; PACA ; cytotoxicity ; nanotoxicology ; high-throughput screening ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 500
    Language English
    Publishing date 2017-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article: Fate and effects of silver nanoparticles on early life-stage development of zebrafish (Danio rerio) in comparison to silver nitrate

    Cambier, Sébastien / Anastasia Georgantzopoulou / Arno C. Gutleb / Camilla Karlsson / Cédric Guignard / Erik Ropstad / Jean-Nicolas Audinot / Lucien Hoffmann / Marcin Kruszewski / Marthe Røgeberg / Steven Verhaegen / Tommaso Serchi / Tore-Geir Iversen

    Science of the total environment. 2018 Jan. 01, v. 610-611

    2018  

    Abstract: The use of silver nanomaterials in everyday products, such as cosmetics, textiles, certain types of packaging, etc. is increasing, leading to their release into the environment, including aquatic ecosystems. This last point initiated this investigation ... ...

    Abstract The use of silver nanomaterials in everyday products, such as cosmetics, textiles, certain types of packaging, etc. is increasing, leading to their release into the environment, including aquatic ecosystems. This last point initiated this investigation on the toxicological effects of Ag nanoparticles (Ag NPs) in the aquatic model organism Danio rerio. For this purpose, zebrafish larvae were exposed to 20nm bare Ag NPs at different concentrations and AgNO3, used as a positive control for Ag+ ions toxicity, at the beginning of their foraging behaviour to determine adverse effects on fitness parameters. We used secondary ion mass spectrometry (SIMS) to determine the localization of Ag and transcriptomics (microarray) to determine the toxicity at the level of gene expression in fish larvae. Exposure to Ag NPs did not result in adverse effects on survival and growth of the fish. However, SIMS analysis showed that Ag NPs mainly concentrate around liver blood vessels and in the interstitial tissue between the intestine and the liver. Gene expression profiles revealed that AgNO3 and Ag NPs impacted common pathways, suggesting similar targets, such as the phototransduction system. However, the Ag NPs showed a broader set of genes impacted following the exposure, including the circadian clock regulation and the photoreception, suggesting specific particle-related effects in addition to those induced by ions.
    Keywords adverse effects ; aquatic ecosystems ; blood vessels ; circadian rhythm ; cosmetics ; Danio rerio ; fabrics ; fish larvae ; foraging ; genes ; intestines ; ions ; liver ; mass spectrometry ; microarray technology ; models ; nanosilver ; packaging ; phototransduction ; silver ; silver nitrate ; toxicity ; transcriptomics
    Language English
    Dates of publication 2018-0101
    Size p. 972-982.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 121506-1
    ISSN 1879-1026 ; 0048-9697
    ISSN (online) 1879-1026
    ISSN 0048-9697
    DOI 10.1016/j.scitotenv.2017.08.115
    Database NAL-Catalogue (AGRICOLA)

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