Citrullination of Proteins: A Common Post-Translational Modification Pathway Induced by Different Nanoparticles
            <i>In Vitro</i>
            and
            <i>In Vivo</i>

Mohamed, Bashir M.; Verma, Navin Kumar; Davies, Anthony M.; McGowan, Aoife; Crosbie-Staunton, Kieran; Prina-Mello, Adriele; Kelleher, Dermot; Botting, Catherine H.; Causey, Corey P.; Thompson, Paul R.; Pruijn, Ger J. M.; Kisin, Elena R.; Tkach, Alexey V.; Shvedova, Anna A.; Volkov, Yuri

doi:10.2217/nnm.11.177

Cited by 80 publications

(73 citation statements)

References 70 publications

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“…14, [18][19][20] Heatmaps graphical illustration in a colorimetric gradient table format was adopted as the most suitable schematic representation to report on any statistical significance and variation from normalized controls based on their Z score value. Heatmap tables illustrate the range of variation of each quantified parameter from the minimum (green) through the mean (yellow) to the maximum (red) according to the parameter under analysis.…”

Section: Discussionmentioning

confidence: 99%

Cellular uptake and biocompatibility of bismuth ferrite harmonic advanced nanoparticles

Staedler

Passemard

Magouroux

et al. 2015

Nanomedicine: Nanotechnology, Biology and Medicine

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Bismuth Ferrite (BFO) nanoparticles (BFO-NP) display interesting optical (nonlinear response) and magnetic properties which make them amenable for bio-oriented diagnostic applications as intra-and extra membrane contrast agents. Due to the relatively recent availability of this material in well dispersed nanometric form, its biocompatibility was not known to date. In this study, we present a thorough assessment of the effects of in vitro exposure of human adenocarcinoma (A549), lung squamous carcinoma (NCI-H520), and acute monocytic leukemia (THP-1) cell lines to uncoated and poly(ethylene glycol)-coated BFO-NP in the form of cytotoxicity, haemolytic response and biocompatibility. Our results support the attractiveness of the functional-BFO towards biomedical applications focused on advanced diagnostic imaging.

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Section: Discussionmentioning

confidence: 99%

Cellular uptake and biocompatibility of bismuth ferrite harmonic advanced nanoparticles

Staedler

Passemard

Magouroux

et al. 2015

Nanomedicine: Nanotechnology, Biology and Medicine

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“…Adhesion of cells on anti-integrin antibody or fibronectin coated surfaces was detected and subsequently quantified using a cell based high content analysis (HCA) system. The assay operates on the principle of fully automated fluorescent microscopy described previously (30)(31)(32) and allows multiplexing of key reporter parameters including cell-adhesion. Untreated or PBOX-15 pre-treated cells were added to fibronectin, anti-α4-, β1-, or β2-integrin antibody coated 24-well or 96-well plates (Nunc, Roskilide, Denmark) at a density of 2x10 5 or 1x10 4 cells/well respectively.…”

Section: Methodsmentioning

confidence: 99%

The microtubule targeting agent PBOX-15 inhibits integrin-mediated cell adhesion and induces apoptosis in acute lymphoblastic leukaemia cells

Lysaght

Verma

Maginn

et al. 2012

International Journal of Oncology

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Abstract. Although recent decades have seen an improved cure rate for newly diagnosed paediatric acute lymphoplastic leukaemia (ALL), the treatment options for adult ALL, T-cell ALL (T-ALL) and relapsed disease remain poor. We have developed a novel series of pyrrolo-1,5-benzoxazepine (PBOX) compounds and established their anticancer efficacy in a variety of human tumour cell types. Here, we demonstrate that PBOX-15 inhibits cell growth, and induces G2/M cell cycle arrest and apoptosis in both T-ALL and B-cell ALL (B-ALL) cells. In addition, prior to PBOX-15-induced apoptosis, PBOX-15 decreases ALL cell adhesion, spreading and migration. Concurrently, PBOX-15 differentially down-regulates β1-, β2-and α4-integrin expression in ALL cells and significantly decreases integrin-mediated cell attachment. PBOX-15 interferes with the lateral mobility and clustering of integrins in both B-ALL and T-ALL cells. These data suggest that PBOX-15 is not only effective in inducing apoptosis in ALL cells, but also has the potential to disrupt integrin-mediated adhesion of malignant lymphocytes, which represents a novel avenue for regulating leukaemic cell homing and migration. IntroductionAcute lymphoblastic leukaemia (ALL) refers to a group of malignancies arising from lymphoid progenitors that may be of B-or T-cell lineage (B-ALL or T-ALL), resulting in proliferation and expansion of lymphoid blasts in bone marrow, blood and other organs. ALL has an overall incidence of 1-1.5 per 100,000 individuals and exhibits a bimodal age distribution with an early peak between ages 2-5 years (4-5 per 100,000 individuals, accounting for 80% of all childhood leukaemia), followed by a second peak after the age of 50 years (1). The treatment of ALL involves complex therapeutic programmes using intensive combination chemotherapy in dose-and timespecific sequences resulting in survival rates greater than 80% in children (2). However, there is a need for novel treatment options as only 30-40% of adults achieve long-term diseasefree survival and both childhood T-ALL and relapsed ALL are associated with poor clinical outcome (3,4).Microtubule targeting agents (MTAs) have been shown to be effective against ALL cells and vincristine is a key component of induction, consolidation and maintenance treatment protocols (3). We have previously described a novel MTA, pyrrolo-1,5-benzoxazepine-15 (PBOX-15), which exhibits anticancer activity against a variety of human tumour cell types, including those derived from both solid and haematological malignancies (5-10). Importantly, PBOX-15 and other related PBOX compounds display minimal toxicity against normal human blood and bone marrow cells, and are well tolerated by both tumour-bearing and healthy mice (7,11).MTA's interference with tubulin dynamics during mitotic spindle formation is well established; however, due to the critical role of microtubules in cell motility and homeostasis, the activity of MTAs may extend beyond inhibition of cytokinesis and subsequent induction of apoptosis. For example, we have...

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“…For example, a multilevel heatmap matrix has been used to illustrate effects of dose, concentration, and time for multiple NMs11, 12, 13 (Figure 1). …”

Section: Experimental Design For Effective High‐throughput Screening:mentioning

confidence: 99%

High throughput toxicity screening and intracellular detection of nanomaterials

Collins

Annangi

Rubio

et al. 2016

WIREs Nanomed Nanobiotechnol

113

106

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With the growing numbers of nanomaterials (NMs), there is a great demand for rapid and reliable ways of testing NM safety—preferably using in vitro approaches, to avoid the ethical dilemmas associated with animal research. Data are needed for developing intelligent testing strategies for risk assessment of NMs, based on grouping and read‐across approaches. The adoption of high throughput screening (HTS) and high content analysis (HCA) for NM toxicity testing allows the testing of numerous materials at different concentrations and on different types of cells, reduces the effect of inter‐experimental variation, and makes substantial savings in time and cost. HTS/HCA approaches facilitate the classification of key biological indicators of NM‐cell interactions. Validation of in vitro HTS tests is required, taking account of relevance to in vivo results. HTS/HCA approaches are needed to assess dose‐ and time‐dependent toxicity, allowing prediction of in vivo adverse effects. Several HTS/HCA methods are being validated and applied for NM testing in the FP7 project NANoREG, including Label‐free cellular screening of NM uptake, HCA, High throughput flow cytometry, Impedance‐based monitoring, Multiplex analysis of secreted products, and genotoxicity methods—namely High throughput comet assay, High throughput in vitro micronucleus assay, and γH2AX assay. There are several technical challenges with HTS/HCA for NM testing, as toxicity screening needs to be coupled with characterization of NMs in exposure medium prior to the test; possible interference of NMs with HTS/HCA techniques is another concern. Advantages and challenges of HTS/HCA approaches in NM safety are discussed. WIREs Nanomed Nanobiotechnol 2017, 9:e1413. doi: 10.1002/wnan.1413For further resources related to this article, please visit the WIREs website.

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Citrullination of Proteins: A Common Post-Translational Modification Pathway Induced by Different Nanoparticles In Vitro and In Vivo

Cited by 80 publications

References 70 publications

Cellular uptake and biocompatibility of bismuth ferrite harmonic advanced nanoparticles

Cellular uptake and biocompatibility of bismuth ferrite harmonic advanced nanoparticles

The microtubule targeting agent PBOX-15 inhibits integrin-mediated cell adhesion and induces apoptosis in acute lymphoblastic leukaemia cells

High throughput toxicity screening and intracellular detection of nanomaterials

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