scholarly journals Comparative evaluation of the impact on endothelial cells induced by different nanoparticle structures and functionalization

2015 ◽  
Vol 6 ◽  
pp. 300-312 ◽  
Author(s):  
Lisa Landgraf ◽  
Ines Müller ◽  
Peter Ernst ◽  
Miriam Schäfer ◽  
Christina Rosman ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Viability ◽  
Research Field ◽  
Size Dependent ◽  
General Rules ◽  
Charged Nanoparticles ◽  
20 Nm ◽  
The Impact ◽  
Insight Into ◽  
Positively Charged

In the research field of nanoparticles, many studies demonstrated a high impact of the shape, size and surface charge, which is determined by the functionalization, of nanoparticles on cell viability and internalization into cells. This work focused on the comparison of three different nanoparticle types to give a better insight into general rules determining the biocompatibility of gold, Janus and semiconductor (quantum dot) nanoparticles. Endothelial cells were subject of this study, since blood is the first barrier after intravenous nanoparticle application. In particular, stronger effects on the viability of endothelial cells were found for nanoparticles with an elongated shape in comparison to spherical ones. Furthermore, a positively charged nanoparticle surface (NH2, CyA) leads to the strongest reduction in cell viability, whereas neutral and negatively charged nanoparticles are highly biocompatible to endothelial cells. These findings are attributed to a rapid internalization of the NH2-functionalized nanoparticles in combination with the damage of intracellular membranes. Interestingly, the endocytotic pathway seems to be a size-dependent process whereas nanoparticles with a size of 20 nm are internalized by caveolae-mediated endocytosis and nanoparticles with a size of 40 nm are taken up by clathrin-mediated internalization and macropinocytosis. Our results can be summarized to formulate five general rules, which are further specified in the text and which determine the biocompatibility of nanoparticles on endothelial cells. Our findings will help to design new nanoparticles with optimized properties concerning biocompatibility and uptake behavior with respect to the respective intended application.

Use of Nano-Formulated Hydroxyurea Enhances Drug Delivery to Pulmonary Artery Endothelial Cells

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4061-4061
Author(s):  
Omar Mohtar ◽  
Doroteja Dragovic ◽  
Jean-Bosco Tagne ◽  
Elizabeth S Klings
Keyword(s):  
Drug Delivery ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Sickle Cell Disease ◽  
Cell Viability ◽  
Sickle Cell ◽  
S Phase ◽  
Cell Disease ◽  
Nano Formulation ◽  
The Impact

Abstract The vasculopathy of sickle cell disease (SCD), characterized by a chronic hemolytic anemia, endothelial dysfunction and recurrent vasoocclusive events, underlies most of the clinical complications. Recent work has suggested that hydroxyurea (HU) enhances endothelial nitric oxide (NO) production and reduces adhesion molecule expression which may contribute to its associated observed reduction in vasoocclusive events and improved survival in SCD. However, clinically HU is under-utilized, at least in part related to medication related toxicity, stressing a need for enhanced drug delivery. The use of nano-emulsions, a class of stable emulsions formed by a monolayer of phospholipids and/or biodegradable material such as chitosan, is a mechanism by which to enhance targeted cellular delivery of therapeutics. We hypothesized that a nano-formulation of HU would enhance drug delivery to the endothelium and may be a direct way of targeting endothelial dysfunction in SCD. Nano-formulated HU (nano-HU) was developed using a phospholipid approach and this compound was found to be biologically stable for > 6 months. Human pulmonary arterial endothelial cells (HPAECs) were co-incubated with 25µM, 125µM and 250µM HU, nano-HU, or the empty nano-emulsification preparation for 48 hours. HPAEC were isolated, and stained with propidium iodide (PI) for cell cycle analysis by FACS. HPAEC treated with 25µM nano-HU demonstrated the highest level of cell viability (55%) and similar levels of S phase inhibition as HPAEC treated with 125µM HU (where 10-20% cell viability was observed). RNA isolation of treated HPAECs was performed and qPCR for VCAM1 and SLX4, a regulator of DNA damage which promotes S phase inhibition was performed. 25µM nano-HU significantly decreased VCAM1 and increased SLX4 expression compared with 25µM HU suggesting increased efficacy at lower levels of toxicity. The impact of nano-HU on endothelial gene expression is currently being evaluated by RNA-seq. Nano-formulation of HU produces a molecule which is highly stable, and able to achieve higher intracellular concentrations with lower rates of toxicity in HPAECs .which provides the opportunity to gain greater understanding of the impact of this medication on the vascular endothelium and the potential for a more targeted and better tolerated delivery of this therapeutic to patients with sickle cell disease. Disclosures Klings: Pfizer: Consultancy.

scholarly journals Vascular and Blood Compatibility of Engineered Cationic Cellulose Nanocrystals in Cell-Based Assays

Nanomaterials ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2072
Author(s):  
Alexandre Bernier ◽  
Tanner Tobias ◽  
Hoang Nguyen ◽  
Shreshth Kumar ◽  
Beza Tuga ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Viability ◽  
Cellulose Nanocrystals ◽  
Blood Compatibility ◽  
Biological Activities ◽  
Umbilical Vein ◽  
Circulatory System ◽  
Dependent Manner ◽  
Umbilical Vein Endothelial Cells ◽  
The Impact

An emerging interest regarding nanoparticles (NPs) concerns their potential immunomodulatory and pro-inflammatory activities, as well as their impact in the circulatory system. These biological activities of NPs can be related to the intensity and type of the responses, which can raise concerns about adverse side effects and limit the biomedical applicability of these nanomaterials. Therefore, the purpose of this study was to investigate the impact of a library of cationic cellulose nanocrystals (CNCs) in the human blood and endothelial cells using cell-based assays. First, we evaluated whether the cationic CNCs would cause hemolysis and aggregation or alteration on the morphology of red blood cells (RBC). We observed that although these nanomaterials did not alter RBC morphology or cause aggregation, at 24 h exposure, a mild hemolysis was detected mainly with unmodified CNCs. Then, we analyzed the effect of various concentrations of CNCs on the cell viability of human umbilical vein endothelial cells (HUVECs) in a time-dependent manner. None of the cationic CNCs caused a dose-response decrease in the cell viability of HUVEC at 24 h or 48 h of exposure. The findings of this study, together with the immunomodulatory properties of these cationic CNCs previously published, support the development of engineered cationic CNCs for biomedical applications, in particular as vaccine nanoadjuvants.

Abstract P802: Potential Sex Differences in Endothelial Cell Death Pathways: Relevance to Stroke Recovery

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Yasir Abdul ◽  
SARAH JAMIL ◽  
Weiguo Li ◽  
Raghavendar Chandran ◽  
Adviye Ergul
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Sex Differences ◽  
Endothelial Cell ◽  
Cell Viability ◽  
Iron Chelation ◽  
Stroke Recovery ◽  
Female Rats ◽  
Male Rats ◽  
The Impact

Introduction: We have shown that iron chelation with deferoxamine (DFX) prevents stroke-induced cerebral vasoregression and improves sensorimotor and cognitive deficits after ischemic stroke in diabetic male rats. Diabetic female rats, on the other hand, develop greater hemorrhagic transformation (HT) but no vasoregression and DFX improves outcomes. HT breakdown products like hemin contribute significantly in secondary inflammation and neuronal death. Given the importance of brain microvascular endothelial cells (BMVECs) on neurovascular restoration in stroke recovery and our previous findings of increased ferroptotic cell death in endothelial cells from male animals, the objectives of this study were to determine 1) the impact of hemin on ferroptotic death in BMVECs of female and male origin, and 2) effect of DFX on ferroptosis. Methods: Male (HBEC5i) and female (BMECd3) human endothelial cell lines were grown in normal conditions. In some experiments cells were treated with hemin (50μM) for 6 hours with and without ferroptosis inhibitor ferrostatin-1 (20μM) or DFX (100μM). Cell viability (MTT and CytoSelect assays), ferroptosis marker proteins and lipid peroxidation (LPO) were assessed. by immunoblotting and, respectively. Results: GPX4 and NRF2 content was decreased with hemin in both sexes while 4HNE immunofluroscence for LPO, a key feature of ferroptosis, was increased. DFX did not prevent hemin-induced changes in GPX4 and ferritin heavy chain in female cells while it was effective in male cells. DFX and ferrostatin-1 improved cell viability in both male and female BMVECs. There were differences in ferrostatin 1 and DFX effects (Table). Conclusions: These results suggest there may be sex differences in how ferroptosis occurs in response to hemin. Better understanding of endothelial ferroptotic cell death regulation and the effect of iron chelation on cell survival can provide novel insights with respect to sex differences in stroke recovery.

MO018QUORUM SENSING MOLECULE INDUCES THE RECEPTOR-INTERACTING PROTEIN KINASE 1-DEPENDENT APOPTOSIS SYNERGISTICALLY WITH LIPOPOLYSACCHARIDE IN ENDOTHELIAL CELLS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Jungho Shin ◽  
Sun Hee Ahn ◽  
Dong-Jin Oh
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Protein Kinase ◽  
Quorum Sensing ◽  
Cell Viability ◽  
Apoptotic Cell ◽  
Umbilical Vein ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Interacting Protein ◽  
The Impact

Abstract Background and Aims Endothelial dysfunction is an initial step for sepsis-associated organ failure. Bacterial quorum sensing molecules play as pathogen-associated molecular patterns, however, the impact of quorum sensing molecules on endothelial cells remains uncertain. This study investigated the molecular mechanism of quorum sensing molecule-induced cell death and the interaction with lipopolysaccharide (LPS) in human umbilical vein endothelial cells. Method Endothelial cells were treated with varying concentrations of N-3-oxododecanoyl-HSL (3OC12-HSL) and LPS derived from Pseudomonas aeruginosa. Results Treatment of 3OC12-HSL reduced cell viability in dose-dependent manners, and the combination of this molecule and LPS exacerbated cell deaths in compared to single treatment of LPS. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay revealed that there were clear increases in apoptotic death following the 3OC12-HSL treatment. Treatment of 3CO12-HSL activated the receptor-interacting protein kinase 1 (RIPK1) pathway, resulting in increases in expression of caspase 8 and caspase 3. Moreover, the combination treatment of LPS and 3OC12-HSL amplified these expressions. Conclusion Treatment of 3OC12-HSL reduces endothelial cell viability, and this effect is synergistical with LPS. 3OC12-HSL induces apoptotic cell death, through the activation of the RIPK1 pathway, moreover, it is amplified in combination with LPS.

scholarly journals Gut Organoid as a New Platform to Study Alginate and Chitosan Mediated PLGA Nanoparticles for Drug Delivery

Marine Drugs ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. 282
Author(s):  
Zahra Davoudi ◽  
Nathan Peroutka-Bigus ◽  
Bryan Bellaire ◽  
Albert Jergens ◽  
Michael Wannemuehler ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Epithelial Cells ◽  
Positive Charge ◽  
Ex Vivo ◽  
Plga Nanoparticles ◽  
Serosal Side ◽  
Coated Nanoparticles ◽  
Charged Nanoparticles ◽  
The Impact ◽  
Positively Charged

Intestinal organoids can be used as an ex vivo epithelial model to study different drug delivery effects on epithelial cells’ luminal surface. In this study, the impact of surface charge on the delivery of 5-ASA loaded PLGA nanoparticles into the lumen of organoids was investigated. Alginate and chitosan were used to coat the nanoparticles and provide negative and positive charges on the particles, respectively. The organoid growth and viability were not affected by the presence of either alginate- or chitosan-coated nanoparticles. It was shown that nanoparticles could be transported from the serosal side of the organoids to the lumen as the dye gradually accumulated in the lumen by day 2–3 after adding the nanoparticles to the Matrigel. By day 5, the dye was eliminated from the lumen of the organoids. It was concluded that the positively charged nanoparticles were more readily transported across the epithelium into the lumen. It may be attributed to the affinity of epithelial cells to the positive charge. Thus, the organoid can be utilized as an appropriate model to mimic the functions of the intestinal epithelium and can be used as a model to evaluate the benefits of nanoparticle-based drug delivery.

Green Synthesized Nanomaterials as Theranostic Platforms for Cancer Treatment: Principles, Challenges and the Road Ahead

2019 ◽  
Vol 26 (8) ◽  
pp. 1311-1327 ◽  
Author(s):  
Pala Rajasekharreddy ◽  
Chao Huang ◽  
Siddhardha Busi ◽  
Jobina Rajkumari ◽  
Ming-Hong Tai ◽  
...  
Keyword(s):  
Nanoparticle Synthesis ◽  
Research Field ◽  
Synthesis Methods ◽  
Synthetic Approach ◽  
Future Directions ◽  
The Road ◽  
New Methods ◽  
Recent Developments ◽  
Theranostic Applications ◽  
Insight Into

With the emergence of nanotechnology, new methods have been developed for engineering various nanoparticles for biomedical applications. Nanotheranostics is a burgeoning research field with tremendous prospects for the improvement of diagnosis and treatment of various cancers. However, the development of biocompatible and efficient drug/gene delivery theranostic systems still remains a challenge. Green synthetic approach of nanoparticles with low capital and operating expenses, reduced environmental pollution and better biocompatibility and stability is a latest and novel field, which is advantageous over chemical or physical nanoparticle synthesis methods. In this article, we summarize the recent research progresses related to green synthesized nanoparticles for cancer theranostic applications, and we also conclude with a look at the current challenges and insight into the future directions based on recent developments in these areas.

VDAC1 Mediated Anticancer Activity of Gallic Acid in Human Lung Adenocarcinoma A549 Cells

2018 ◽  
Vol 18 (2) ◽  
pp. 255-262 ◽  
Author(s):  
Aikebaier Maimaiti ◽  
Amier Aili ◽  
Hureshitanmu Kuerban ◽  
Xuejun Li
Keyword(s):  
Western Blot ◽  
Cell Viability ◽  
Gallic Acid ◽  
Molecular Mechanisms ◽  
A549 Cells ◽  
Dependent Manner ◽  
Lung Carcinoma Cells ◽  
Induced Apoptosis ◽  
The Impact

Aims: Gallic acid (GA) is generally distributed in a variety of plants and foods, and possesses cell growth-inhibiting activities in cancer cell lines. In the present study, the impact of GA on cell viability, apoptosis induction and possible molecular mechanisms in cultured A549 lung carcinoma cells was investigated. Methods: In vitro experiments showed that treating A549 cells with various concentrations of GA inhibited cell viability and induced apoptosis in a dose-dependent manner. In order to understand the mechanism by which GA inhibits cell viability, comparative proteomic analysis was applied. The changed proteins were identified by Western blot and siRNA methods. Results: Two-dimensional electrophoresis revealed changes that occurred to the cells when treated with or without GA. Four up-regulated protein spots were clearly identified as malate dehydrogenase (MDH), voltagedependent, anion-selective channel protein 1(VDAC1), calreticulin (CRT) and brain acid soluble protein 1(BASP1). VDAC1 in A549 cells was reconfirmed by western blot. Transfection with VDAC1 siRNA significantly increased cell viability after the treatment of GA. Further investigation showed that GA down regulated PI3K/Akt signaling pathways. These data strongly suggest that up-regulation of VDAC1 by GA may play an important role in GA-induced, inhibitory effects on A549 cell viability.

Empathy as moderator of gender differences in Chinese insurance agents' business ethical sensitivity

2017 ◽  
Vol 45 (6) ◽  
pp. 1029-1042 ◽  
Author(s):  
Na Zhang ◽  
Jian Zhang ◽  
Jing Wang
Keyword(s):  
Gender Differences ◽  
Business Ethics ◽  
Research Field ◽  
Ethical Sensitivity ◽  
Men And Women ◽  
Insurance Agents ◽  
Factors Associated ◽  
Ethics Research ◽  
The Relationship ◽  
Insight Into

To expand the business ethics research field, and to increase society's understanding of Chinese insurance agents' business ethics, we investigated how gender differences are related to agents' business ethical sensitivity and whether or not these relationships are moderated by empathy. Through a regression analysis of the factors associated with the business ethical sensitivity of 417 Chinese insurance agents, we found that gender played an important role in affecting business ethical sensitivity, and empathy significantly affected business ethical sensitivity. Furthermore, empathy had a moderating effect on the relationship between gender and business ethical sensitivity. Both men and women with strong empathy scored high on business ethical sensitivity; however, men with strong empathy had higher levels of business ethical sensitivity than did women with little empathy. The findings add to the literature by providing insight into the mechanisms responsible for the benefits of empathy in increasing business ethical sensitivity.

The Interaction of Judicial and Legislative Policymaking

2018 ◽  
Author(s):  
Susanne K. Schmidt
Keyword(s):  
Mutual Recognition ◽  
Case Law ◽  
Legislative Process ◽  
European Legislation ◽  
Eu Legislation ◽  
Political Preferences ◽  
General Rules ◽  
Judicial Policymaking ◽  
The Impact ◽  
The Eu

Chapter 4 systematizes the different ways that judicial policymaking can have an impact on European legislation. Identifying the codification of case-law principles in secondary law contributes to research on the EU in two important ways: it shows how EU legislation is embedded in case-law development, and that the impact of case law cannot be reduced to the question of compliance with single rulings. A differentiation is made between several types of judicial ‘shadow’ over the legislative process. Then the Services Directive and the regulation on the mutual recognition of goods are analysed. The principles of case law that were motivated by the specific circumstances of individual cases constrain the design of general rules. Secondary law cannot modify constitutional principles. At best, the legislature can hope to signal its political preferences to the Court.

scholarly journals Changing landscapes: Gay men in the west and northwest of Ireland

Sexualities ◽  
2020 ◽  
pp. 136346072098169
Author(s):  
Aidan McKearney
Keyword(s):  
Gay Men ◽  
Social Rights ◽  
Irish Society ◽  
Recent Past ◽  
Same Sex ◽  
Lgbt People ◽  
The Many ◽  
Northwest Region ◽  
The Impact ◽  
Insight Into

This article focuses on the experiences of gay men in the rural west and northwest region of Ireland, during a period of transformational social and political change in Irish society. These changes have helped facilitate new forms of LGBTQI visibility, and local radicalism in the region. Same-sex weddings, establishment of rural LGBT groups and marching under an LGBT banner at St Patricks Day parades would have been unthinkable in the recent past; but they are now becoming a reality. The men report continuing challenges in their lives as gay men in the nonmetropolitan space, but the emergence of new visibility, voice and cultural acceptance of LGBT people is helping change their lived experiences. The study demonstrates the impact of local activist LGBT citizens. Through their testimonies we can gain an insight into the many, varied and interwoven factors that have interplayed to create the conditions necessary for the men to: increasingly define themselves as gay to greater numbers of people in their localities; to embrace greater visibility and eschew strategies of silence; and aspire to a host of legal, political, cultural and social rights including same-sex marriage. Organic forms of visibility and local radicalism have emerged in the region and through an analysis of their testimonies we can see how the men continue to be transformed by an ever-changing landscape.

Sign in / Sign up

Export Citation Format

Share Document