Role of purinergic receptors in platelet-nanoparticle interactions
TL;DR: The nanoparticles, composed of various materials and shape features, are likely to impart a pro-aggregatory response in platelets, and the fact that the response was absent in the case of P2Y12 blocked subjects (CdS nanoparticles being an exception) suggests that the low-affinity P2y12 receptor may be an important target for the nanoparticles.
Abstract: Primary objective. Elevation of the thrombotic responses mediated by a variety of carbon-derived nanoparticles was recently reported in the literature. In this paper our objective was to investigate whether metal nanoparticles (iron, copper, gold or cadmium sulfide [CdS]) impart such prothrombotic effects on human platelets. Secondly, we wanted to examine whether such effects were mediated through any specific platelet receptor. Experimental design. The size distributions and zeta potentials of characterized gold, copper, iron and CdS (rod & sphere) nanoparticles were measured using photon correlation spectroscopy and laser Doppler velocimetry. The effect of two classes of agonists, adenosine diphosphate (ADP) and epinephrine were studied. To study the effect of ADP, a suboptimal concentration was chosen below a critical concentration. Above the critical concentration, the aggregation assumed its standard hyperbolic shape (and de-aggregation disappeared). Pro-aggregatory action of a given agent can be und...
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TL;DR: The proposed drug delivery strategy may lead to clinical improvement in the management of cancer treatment as lower drug concentration can be used in a targeted mode and the method can be personalized as patient's own platelet can be use for deliver various drugs.
Abstract: Purpose
To develop an efficient biocompatible and targeted drug delivery system in which platelets, an essential blood component having a natural affinity for cancer cells, are used as carrier of anticancer drug as delivery of drug to the targeted site is crucial for cancer treatment.
62 citations
Cites background from "Role of purinergic receptors in pla..."
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TL;DR: It is shown that AuNP response can provide a simple measure for thrombotic risk associated with nano-drugs and platelet aggregation can be triggered in the presence of gold nanoparticles (AuNP).
Abstract: The nanoparticle (NP) response of platelets is shown to be critically dependent on extent of preactivation of platelets by an agonist like ADP. A transition from de-aggregatory to aggregatory state is triggered in the presence of gold NPs (AuNP) only in such critical conditions. Adhered and suspended platelets respond differentially to NPs. Preactivation in the adhered state induced by shear force explains such observation. The NP effect is associated with enhanced release reaction, tyrosine phosphorylation and CD62P expression level. Unlike cancer cells, whose response is maximal when NP size is optimal (within the range 50 - 70 nm), the platelet response monotonically increases with reduction of the AuNP size. The uptake study, using quenching of quinacrine hydrochloride fluorescence by AuNP, indicates that accumulation 18 nm AuNP is several-fold higher than the 68 nm AuNP. It is further shown that AuNP response can provide a simple measure for thrombotic risk associated with nano-drugs. From the Clinical Editor Platelet aggregation can be triggered in the presence of gold nanoparticles (AuNP). Platelet response monotonically increases with reduction of the AuNP size. AuNP response can provide a simple measure for thrombotic risk associated with nano-drugs.
61 citations
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TL;DR: In this paper, the effect of nanomaterials on platelet activation and aggregation was investigated, and it was found that even small amounts of nanoparticles in the bloodstream might contribute to the development of thrombosis, indicating that nanoparticles unable to trigger appreciable responses can synergize with sub-threshold amounts of physiological agonists to mediate platelet aggregation.
Abstract: Nanomaterials are attracting growing interest for their potential use in several applications as nanomedicine; therefore, the analysis of their potential toxic effects on various cellular models, including circulating blood cells, is mandatory. This study aimed to investigate the effect of three unrelated nanomaterials, namely nanoscale silica, multiwalled carbon nanotubes, and carbon black, on platelet activation and aggregation. We found that these nanomaterials stimulate some of the typical biochemical pathways involved in canonical platelet activation, such as the stimulation of phospholipase C and Rap1b, resulting in the integrin α IIb β 3 -mediated platelet aggregation, through a mechanism largely dependent on the release of the extracellular second messengers ADP and thromboxane A 2 . Importantly, we found that doses of nanoparticles unable to trigger appreciable responses can synergize with subthreshold amounts of physiological agonists to mediate platelet aggregation, indicating that even small amounts of nanomaterials in the bloodstream might contribute to the development of thrombosis. From the Clinical Editor In this study, nanosized particles of three virtually unrelated materials (silica, multi-walled carbon nanotubes and carbon black) were investigated regarding their effects on platelet activation and aggregation. All were found to stimulate some of the typical biochemical pathways involved in canonical platelet activation, and were found to have synergistic effects with physiologic platelet activator agonists.
43 citations
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01 Jan 2012
TL;DR: It is found that doses of nanoparticles unable to trigger appreciable responses can synergize with subthreshold amounts of physiological agonists to mediate platelet aggregation, indicating that even small amounts of nanomaterials in the bloodstream might contribute to the development of thrombosis.
Abstract: Nanomaterials are attracting growing interest for their potential use in several applications as nanomedicine; therefore, the analysis of their potential toxic effects on various cellular models, including circulating blood cells, is mandatory. This study aimed to investigate the effect of three unrelated nanomaterials, namely nanoscale silica, multiwalled carbon nanotubes, and carbon black, on platelet activation and aggregation. We found that these nanomaterials stimulate some of the typical biochemical pathways involved in canonical platelet activation, such as the stimulation of phospholipase C and Rap1b, resulting in the integrin αIIbβ3-mediated platelet aggregation, through a mechanism largely dependent on the release of the extracellular second messengers ADP and thromboxane A2. Importantly, we found that doses of nanoparticles unable to trigger appreciable responses can synergize with subthreshold amounts of physiological agonists to mediate platelet aggregation, indicating that even small amounts of nanomaterials in the bloodstream might contribute to the development of thrombosis. From the Clinical Editor: In this study, nanosized particles of three virtually unrelated materials (silica, multi-walled carbon nanotubes and carbon black) were investigated regarding their effects on platelet activation and aggregation. All were found to stimulate some of the typical biochemical pathways involved in canonical platelet activation, and were found to have synergistic effects with physiologic platelet activator agonists.
38 citations
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TL;DR: The main objective of the present work was to study how platelet functions were changed in the presence of different nano-surface or surface capping, which may provide a measure for the safety of a nanoparticle, and also assess the use of such nanoparticles in platelet modulation.
Abstract: Metallic nanoparticles are attractive candidates as MRI contrast agents and mediators for drug delivery, diagnostics, and therapy. Direct contact and exposure to blood circulation is common in many such applications. The consequent thrombotic response may therefore be important to study. The main objective of the present work was to study how platelet functions were changed in the presence of different nano-surface or surface capping, which may provide a measure for the safety of a nanoparticle, and also assess the use of such nanoparticles in platelet modulation. Aggregometry, ATP release reaction, flow cytometry and immune-blotting studies were performed to study platelet response to different nano-particles (iron oxide, gold and silver). For each nanoparticle surface conjugation (capping) was varied. It was found that citric acid functionalized iron oxide nanoparticles have anti-platelet activity, with a decrease in aggregation, tyrosine phosphorylation level, and granule release. On the other hand in other cases (e.g. gold nanoparticles) pro-aggregatory response was observed in the presence of nanoparticles and, in some cases, the nanoparticles behaved neutrally (e.g. for starch-coated iron oxide nanoparticles). Therefore, nanoparticles can induce antiplatelet or a pro-aggregatory response, or remain neutral depending on surface capping. A related observation is that antiplatelet drugs can be made more potent by nanoparticle conjugation.
28 citations
References
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TL;DR: Fine particulate and sulfur oxide--related pollution were associated with all-cause, lung cancer, and cardiopulmonary mortality and long-term exposure to combustion-related fine particulate air pollution is an important environmental risk factor for cardiopULmonary and lung cancer mortality.
Abstract: ContextAssociations have been found between day-to-day particulate air pollution
and increased risk of various adverse health outcomes, including cardiopulmonary
mortality. However, studies of health effects of long-term particulate air
pollution have been less conclusive.ObjectiveTo assess the relationship between long-term exposure to fine particulate
air pollution and all-cause, lung cancer, and cardiopulmonary mortality.Design, Setting, and ParticipantsVital status and cause of death data were collected by the American
Cancer Society as part of the Cancer Prevention II study, an ongoing prospective
mortality study, which enrolled approximately 1.2 million adults in 1982.
Participants completed a questionnaire detailing individual risk factor data
(age, sex, race, weight, height, smoking history, education, marital status,
diet, alcohol consumption, and occupational exposures). The risk factor data
for approximately 500 000 adults were linked with air pollution data
for metropolitan areas throughout the United States and combined with vital
status and cause of death data through December 31, 1998.Main Outcome MeasureAll-cause, lung cancer, and cardiopulmonary mortality.ResultsFine particulate and sulfur oxide–related pollution were associated
with all-cause, lung cancer, and cardiopulmonary mortality. Each 10-µg/m3 elevation in fine particulate air pollution was associated with approximately
a 4%, 6%, and 8% increased risk of all-cause, cardiopulmonary, and lung cancer
mortality, respectively. Measures of coarse particle fraction and total suspended
particles were not consistently associated with mortality.ConclusionLong-term exposure to combustion-related fine particulate air pollution
is an important environmental risk factor for cardiopulmonary and lung cancer
mortality.
7,264 citations
"Role of purinergic receptors in pla..." refers background in this paper
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TL;DR: In this new nanoparticle-based detection system, Au particles are used to complex a 24-base polynucleotide target and exhibit characteristic, exceptionally sharp “melting transitions” which allows one to distinguish target sequences that contain one base end mismatches, deletions, or an insertion from the fully complementary target.
Abstract: Selective colorimetric polynucleotide detection based on Au nanoparticle probes which align in a “tail-to-tail” fashion onto a target polynucleotide is described. In this new nanoparticle-based detection system, Au particles (∼13 nm diameter), which are capped with 3‘- and 5‘-(alkanethiol)oligonucleotides, are used to complex a 24-base polynucleotide target. Hybridization of the target with the probes results in the formation of an extended polymeric Au nanoparticle/polynucleotide aggregate, which triggers a red to purple color change in solution. The color change is due to a red shift in the surface plasmon resonance of the Au nanoparticles. The aggregates exhibit characteristic, exceptionally sharp “melting transitions” (monitored at 260 or 700 nm), which allows one to distinguish target sequences that contain one base end mismatches, deletions, or an insertion from the fully complementary target. When test solutions are spotted onto a C18 reverse-phase thin-layer chromatography plate, color differentia...
2,185 citations
"Role of purinergic receptors in pla..." refers methods in this paper
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TL;DR: Nanoscale iron particles represent a new generation of environmental remediation technologies that could provide cost-effective solutions to some of the most challenging environmental cleanup problems as mentioned in this paper, and they provide enormous flexibility for in situ applications.
Abstract: Nanoscale iron particles represent a new generation of environmental remediation technologies that could provide cost-effective solutions to some of the most challenging environmental cleanup problems. Nanoscale iron particles have large surface areas and high surface reactivity. Equally important, they provide enormous flexibility for in situ applications. Research has shown that nanoscale iron particles are very effective for the transformation and detoxification of a wide variety of common environmental contaminants, such as chlorinated organic solvents, organochlorine pesticides, and PCBs. Modified iron nanoparticles, such as catalyzed and supported nanoparticles have been synthesized to further enhance the speed and efficiency of remediation. In this paper, recent developments in both laboratory and pilot studies are assessed, including: (1) synthesis of nanoscale iron particles (10–100nm, >99.5% Fe) from common precursors such as Fe(II) and Fe(III); (2) reactivity of the nanoparticles towards contaminants in soil and water over extended periods of time (e.g., weeks); (3) field tests validating the injection of nanoparticles into aquifer, and (4) in situ reactions of the nanoparticles in the subsurface.
1,834 citations
"Role of purinergic receptors in pla..." refers background in this paper
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TL;DR: In this paper, the authors estimated the impact of outdoor and traffic-related air pollution on public health in Austria, France, and Switzerland, and found that air pollution contributes to mortality and morbidity.
Abstract: Background: Air pollution contributes to mortality and morbidity. We estimated the impact of outdoor (total) and traffic-related air pollution on public health in Austria, France, and Switzerland. Attributable cases of morbidity and mortality were estimated. Methods: Epidemiology-based exposure-response functions for a 10 μg/m3 increase in particulate matter (PM10) were used to quantify the effects of air pollution. Cases attributable to air pollution were estimated for mortality (adults \textgreater30 years), respiratory and cardiovascular hospital admissions (all ages), incidence of chronic bronchitis (adults \textgreater25 years), bronchitis episodes in children (\textless15 years), restricted activity days (adults \textgreater20 years), and asthma attacks in adults and children. Population exposure (PM10) was modelled for each km2. The traffic-related fraction was estimated based on PM10 emission inventories. Findings: Air pollution caused 6% of total mortality or more than 40 000 attributable cases per year. About half of all mortality caused by air pollution was attributed to motorised traffic, accounting also for: more than 25 000 new cases of chronic bronchitis (adults); more than 290 000 episodes of bronchitis (children); more than 0·5 million asthma attacks; and more than 16 million person-days of restricted activities. Interpretation: This assessment estimates the public-health impacts of current patterns of air pollution. Although individual health risks of air pollution are relatively small, the public-health consequences are considerable. Traffic-related air pollution remains a key target for public-health action in Europe. Our results, which have also been used for economic valuation, should guide decisions on the assessment of environmental health-policy options.
1,533 citations