scholarly journals Molecular and Cellular Risk Assessment of Healthy Human Cells and Cancer Human Cells Exposed to Nanoparticles

2019 ◽  
Vol 21 (1) ◽  
pp. 230 ◽  
Author(s):  
Edward Helal-Neto ◽  
Aline Oliveira da Silva de Barros ◽  
Roberta Saldanha-Gama ◽  
Renata Brandão-Costa ◽  
Luciana Magalhães Rebêlo Alencar ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Polymeric Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Colon Adenocarcinoma ◽  
Magnetic Core ◽  
Human Cells ◽  
The Body ◽  
Healthy Human ◽  
Lack Of Information ◽  
Great Debate

Nanodrugs have in recent years been a subject of great debate. In 2017 alone, almost 50 nanodrugs were approved for clinical use worldwide. Despite the advantages related to nanodrugs/nanomedicine, there is still a lack of information regarding the biological safety, as the real behavior of these nanodrugs in the body. In order to better understand these aspects, in this study, we evaluated the effect of polylactic acid (PLA) nanoparticles (NPs) and magnetic core mesoporous silica nanoparticles (MMSN), of 1000 nm and 50 nm, respectively, on human cells. In this direction we evaluated the cell cycle, cytochemistry, proliferation and tubulogenesis on tumor cells lines: from melanoma (MV3), breast cancer (MCF-7, MDA-MB-213), glioma (U373MG), prostate (PC3), gastric (AGS) and colon adenocarcinoma (HT-29) and non-tumor cell lines: from human melanocyte (NGM), fibroblast (FGH) and endothelial (HUVEC), respectively. The data showed that an acute exposure to both, polymeric nanoparticles or MMSN, did not show any relevant toxic effects on neither tumor cells nor non-tumor cells, suggesting that although nanodrugs may present unrevealed aspects, under acute exposition to human cells they are harmless.

scholarly journals Modulation of Macrophages M1/M2 Polarization Using Carbohydrate-Functionalized Polymeric Nanoparticles

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 88
Author(s):  
Raquel G. D. Andrade ◽  
Bruno Reis ◽  
Benjamin Costas ◽  
Sofia A. Costa Lima ◽  
Salette Reis
Keyword(s):  
Inflammatory Responses ◽  
Polymeric Nanoparticles ◽  
Interaction Mechanism ◽  
Mannose Receptor ◽  
The Body ◽  
Receptor Expression ◽  
Production Methods ◽  
Polymeric Nanocarriers ◽  
Efficient Delivery

Exploiting surface endocytosis receptors using carbohydrate-conjugated nanocarriers brings outstanding approaches to an efficient delivery towards a specific target. Macrophages are cells of innate immunity found throughout the body. Plasticity of macrophages is evidenced by alterations in phenotypic polarization in response to stimuli, and is associated with changes in effector molecules, receptor expression, and cytokine profile. M1-polarized macrophages are involved in pro-inflammatory responses while M2 macrophages are capable of anti-inflammatory response and tissue repair. Modulation of macrophages’ activation state is an effective approach for several disease therapies, mediated by carbohydrate-coated nanocarriers. In this review, polymeric nanocarriers targeting macrophages are described in terms of production methods and conjugation strategies, highlighting the role of mannose receptor in the polarization of macrophages, and targeting approaches for infectious diseases, cancer immunotherapy, and prevention. Translation of this nanomedicine approach still requires further elucidation of the interaction mechanism between nanocarriers and macrophages towards clinical applications.

scholarly journals Gene-Directed Enzyme Prodrug Therapy by Dendrimer-Like Mesoporous Silica Nanoparticles against Tumor Cells

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1298
Author(s):  
Vicente Candela-Noguera ◽  
Gema Vivo-Llorca ◽  
Borja Díaz de Greñu ◽  
María Alfonso ◽  
Elena Aznar ◽  
...  
Keyword(s):  
Cell Death ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Tumor Cells ◽  
Mesoporous Silica Nanoparticles ◽  
Combined Treatment ◽  
Bond Rupture ◽  
Enzyme Prodrug Therapy ◽  
Bacterial Gene ◽  
Reducing Environment

We report herein a gene-directed enzyme prodrug therapy (GDEPT) system using gated mesoporous silica nanoparticles (MSNs) in an attempt to combine the reduction of side effects characteristic of GDEPT with improved pharmacokinetics promoted by gated MSNs. The system consists of the transfection of cancer cells with a plasmid controlled by the cytomegalovirus promoter, which promotes β-galactosidase (β-gal) expression from the bacterial gene lacZ (CMV-lacZ). Moreover, dendrimer-like mesoporous silica nanoparticles (DMSNs) are loaded with the prodrug doxorubicin modified with a galactose unit through a self-immolative group (DOXO-Gal) and modified with a disulfide-containing polyethyleneglycol gatekeeper. Once in tumor cells, the reducing environment induces disulfide bond rupture in the gatekeeper with the subsequent DOXO-Gal delivery, which is enzymatically converted by β-gal into the cytotoxic doxorubicin drug, causing cell death. The combined treatment of the pair enzyme/DMSNs-prodrug are more effective in killing cells than the free prodrug DOXO-Gal alone in cells transfected with β-gal.

Janus Mesoporous Silica Nanoparticles for Dual Targeting of Tumor Cells and Mitochondria

2017 ◽  
Vol 9 (32) ◽  
pp. 26697-26706 ◽  
Author(s):  
Victoria López ◽  
Maria Rocío Villegas ◽  
Verónica Rodríguez ◽  
Gonzalo Villaverde ◽  
Daniel Lozano ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Tumor Cells ◽  
Mesoporous Silica Nanoparticles ◽  
Dual Targeting

Medicine: Experimentation, Politics, Emergent Bodies

2012 ◽  
Vol 18 (3-4) ◽  
pp. 1-17 ◽  
Author(s):  
Mike Michael ◽  
Marsha Rosengarten
Keyword(s):  
Public Health Policy ◽  
Science And Technology Studies ◽  
Controlled Trial ◽  
Judith Butler ◽  
The Body ◽  
The Political ◽  
Medical Evidence ◽  
Special Issue ◽  
Healthy Human ◽  
Randomized Controlled

In this introduction, we address some of the complexities associated with the emergence of medicine’s bodies, not least as a means to ‘working with the body’ rather than simply producing a critique of medicine. We provide a brief review of some of the recent discussions on how to conceive of medicine and its bodies, noting the increasing attention now given to medicine as a technology or series of technologies active in constituting a multiplicity of entities – bodies, diseases, experimental objects, the individualization of responsibility for health and even the precarity of life. We contrast what feminist theorists in the tradition of Judith Butler have referred to as the question of matter, and Science and Technology Studies with its focus on practice and the nature of emergence. As such we address tensions that exist in analyses of the ontological status of ‘the body’ – human and non-human – as it is enacted in the work of the laboratory, the randomized controlled trial, public health policy and, indeed, the market that is so frequently entangled with these spaces. In keeping with the recent turns toward ontology and affect, we suggest that we can regard medicine as concerned with the contraction and reconfiguration of the body’s capacities to affect and be affected, in order to allow for the subsequent proliferation of affects that, according to Bruno Latour, marks corporeal life. Treating both contraction and proliferation circumspectly, we focus on the patterns of affects wrought in particular by the abstractions of medicine that are described in the contributions to this special issue. Drawing on the work of A.N. Whitehead, we note how abstractions such as ‘medical evidence’, the ‘healthy human body’ or the ‘animal model’ are at once realized and undercut, mediated and resisted through the situated practices that eventuate medicine’s bodies. Along the way, we touch on the implications of this sort of perspective for addressing the distribution of agency and formulations of the ethical and the political in the medical eventuations of bodies.

scholarly journals Epithelial-Mesenchymal Transition and Metastasis under the Control of Transforming Growth Factor β

2018 ◽  
Vol 19 (11) ◽  
pp. 3672 ◽  
Author(s):  
Yutaro Tsubakihara ◽  
Aristidis Moustakas
Keyword(s):  
Growth Factor ◽  
Tumor Cells ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Transforming Growth Factor Β ◽  
Basement Membranes ◽  
The Body ◽  
Common Denominator ◽  
Adhesion Forces ◽  
Mesenchymal Transition

Metastasis of tumor cells from primary sites of malignancy to neighboring stromal tissue or distant localities entails in several instances, but not in every case, the epithelial-mesenchymal transition (EMT). EMT weakens the strong adhesion forces between differentiated epithelial cells so that carcinoma cells can achieve solitary or collective motility, which makes the EMT an intuitive mechanism for the initiation of tumor metastasis. EMT initiates after primary oncogenic events lead to secondary secretion of cytokines. The interaction between tumor-secreted cytokines and oncogenic stimuli facilitates EMT progression. A classic case of this mechanism is the cooperation between oncogenic Ras and the transforming growth factor β (TGFβ). The power of TGFβ to mediate EMT during metastasis depends on versatile signaling crosstalk and on the regulation of successive waves of expression of many other cytokines and the progressive remodeling of the extracellular matrix that facilitates motility through basement membranes. Since metastasis involves many organs in the body, whereas EMT affects carcinoma cell differentiation locally, it has frequently been debated whether EMT truly contributes to metastasis. Despite controversies, studies of circulating tumor cells, studies of acquired chemoresistance by metastatic cells, and several (but not all) metastatic animal models, support a link between EMT and metastasis, with TGFβ, often being a common denominator in this link. This article aims at discussing mechanistic cases where TGFβ signaling and EMT facilitate tumor cell dissemination.

scholarly journals A Computational and Literature-Based Evaluation for a Combination of Chiral Anti-CoV Drugs to Block and Eliminate SARS-CoV-2 Safely

2021 ◽  
Author(s):  
Mohd. Suhail
Keyword(s):  
Side Effects ◽  
Jc Virus ◽  
Computational Study ◽  
Human Cells ◽  
The Body ◽  
Binding Affinities ◽  
Chiral Drugs ◽  
Main Protease ◽  
The World ◽  
Second Wave

<p><a>It has been a great challenge for scientists to develop an anti-covid drug/vaccine with fewer side effects, since the coronavirus began. Of course, the prescription of chiral drugs (chloroquine or hydroxychloroquine) has been proved wrong because these chiral drugs neither kill the virus nor eliminate it from the body, but block SARS-CoV-2 from binding to human cells. Another hurdle in front of the world, is not only the positive test of the patient recovered from coronavirus but also the second wave of Covid 19. Hence, the word demands such a drug or drug combination which not only prevents the entry of SARS-CoV-2 in the human cell but also eliminates it or its material from the body completely. The presented computational study explains (i) why the prescription of chiral drugs was not satisfactory (ii) what types of modification can make their prescription satisfactory (iii) the mechanism of action of chiral drugs (chloroquine and hydroxychloroquine) to block SARS-CoV-2 from binding to human cells, and (iv) the strength of mefloquine to eliminate SARS-CoV-2. As the main protease (M<b><sup>pro</sup></b>) of microbes is considered as an effective target for drug design and development, the binding affinities of mefloquine with the main proteases (M<sup>pros</sup>) of JC virus and SARS-CoV-2, were calculated, and then compared to know the eliminating strength of mefloquine against SARS-CoV-2. The main protease (M<sup>pro</sup>) of JC virus was taken because mefloquine has already shown a tremendous result of eliminating it from the body. The current study includes the docking results and literature data in support of the prescription of a combination of S-(+)-hydroxychloroquine and (+) mefloquine. Besides, the presented study also confirms that the prescription of only hydroxychloroquine would not be so effective as in combined form with mefloquine.</a></p>

scholarly journals Multiple-Responsive Mesoporous Silica Nanoparticles for Highly Accurate Drugs Delivery to Tumor Cells

ACS Omega ◽  
2018 ◽  
Vol 3 (4) ◽  
pp. 4306-4315 ◽  
Author(s):  
Ronghua Jin ◽  
Zhongning Liu ◽  
Yongkang Bai ◽  
Yongsheng Zhou ◽  
Xin Chen
Keyword(s):  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Tumor Cells ◽  
Mesoporous Silica Nanoparticles

Mutual effects of free and nanoencapsulated phenolic compounds on human microbiota

2021 ◽  
Vol 28 ◽  
Author(s):  
Carina Cassini ◽  
Pedro Henrique Zatti ◽  
Valéria Weiss Angeli ◽  
Catia Santos Branco ◽  
Mirian Salvador
Keyword(s):  
Phenolic Compounds ◽  
Gut Microbiota ◽  
Oral Bioavailability ◽  
Polymeric Nanoparticles ◽  
The Body ◽  
Biological Targets ◽  
Chemical Structures ◽  
Metabolic Transformation ◽  
Biological Performance ◽  
The Impact

: Phenolic compounds (PC) have many health benefits such as antioxidant, anticarcinogenic, neuroprotective, and anti-inflammatory activities. All of these activities depend on their chemical structures and their interaction with biological targets in the body. PC occur naturally in polymerized form, linked to glycosides and requires metabolic transformation from their ingestion to their absorption. The gut microbiota can transform PC into more easily absorbed metabolites. The PC, in turn, have prebiotic and antimicrobial actions on the microbiota. Despite this, their low oral bioavailability still compromises biological performance. Therefore, the use of nanocarriers has been demonstrated to be a useful strategy to improve PC absorption and, consequently, their health effects. Nanotechnology is an excellent alternative able to overcome the limits of oral bioavailability of PC, since it offers protection from degradation during their passage through the gastrointestinal tract. Moreover, nanotechnology is also capable of promoting controlled PC release and modulating the interaction between PC and the microbiota. However, little is known about the impact of the nanotechnology on PC effects on the gut microbiota. This review highlights the use of nanotechnology for PC delivery on gut microbiota, focusing on the ability of such formulations to enhance oral bioavailability by applying nanocarriers (polymeric nanoparticles, nanostructured lipid carriers, solid lipid nanoparticles). In addition, the effects of free and nanocarried PC or nanocarriers per se on gut microbiota are also described.

ANP kinetics in normal men: in vivo measurement by a tracer method and correlation with sodium intake

1993 ◽  
Vol 264 (3) ◽  
pp. F480-F489 ◽  
Author(s):  
G. Iervasi ◽  
A. Clerico ◽  
S. Berti ◽  
A. Pilo ◽  
F. Vitek ◽  
...  
Keyword(s):  
High Performance ◽  
Sodium Intake ◽  
Mean Transit Time ◽  
Normal Subjects ◽  
The Body ◽  
Metabolic Clearance ◽  
Healthy Human ◽  
Large Space ◽  
Wide Range

125I-labeled atrial natriuretic peptide (ANP) was bolus injected into seven healthy human male subjects on an unrestricted diet (sodium intake ranging from 80 to 300 mmol/day). A high-performance liquid chromatographic procedure was used to purify the labeled hormone and the principal labeled metabolites in venous plasma samples collected up to 50 min after injection. The main ANP kinetic parameters were derived from the disappearance curves of the 125I-ANP, which were satisfactorily fitted by a biexponential function in all subjects. Newly produced ANP initially distributes in a large space (plasma-equivalent volume is 12.1 +/- 3.6 l/m2 body surface); the hormone rapidly leaves this sampling space through both degradation and distribution in peripheral spaces, as indicated by the single-pass mean transit time through the sampling space (3.9 +/- 1.2 min). The mean residence time in the body (22.7 +/- 23.1 min) and the plasma-equivalent total distribution volume (30.9 +/- 12.0 l/m2) indicate that ANP is also widely distributed outside the initial space. Metabolic clearance rate (MCR) values were distributed across a wide range (from 740 to 2,581 ml.min-1 x m-2) and were shown to correlate strongly with the daily urinary excretion of sodium. These results indicate that: 1) newly produced ANP is rapidly distributed and degraded, 2) the body pool of the hormone can be considered as a combination of two exchanging spaces, 3) circulating ANP is < or = 1/15 of the body pool, and 4) MCR of ANP is closely related to sodium intake, at least in normal subjects on a free sodium intake diet.

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