1,720,974 research outputs found
Size and charge of nanoparticles following incubation with human plasma of healthy and pancreatic cancer patients
No full textWhen nanoparticles (NPs) enter a biological environment, proteins bind to their surface forming a protein coating, which alters NP features giving it a biological identity, which controls its physiological response. The NP biological identity (size, charge and aggregation state) does strictly correlate with its physicochemical properties and the nature of the biological environment. While the former relationship has been extensively investigated, whether and how alterations in the physiological environment affect the biological identity of the NPs remains unclear. In this work we enrolled healthy and histologically proven pancreatic cancer patients. A statistically significant reduction in the level of clinically relevant proteins in cancer patients occurred. Positively and negatively charged lipid nanoparticles with two different surface chemistries (plain and PEGylated) were incubated with human plasma from both groups and characterized thoroughly by dynamic light scattering and zeta potential measurements. Only when plain positively charged NPs were tested, significant difference in zeta-potential between healthy and pancreatic cancer groups was found. This result implies that pooling human plasma from healthy volunteers might lead to a bias and thus unpredictable consequences in regard to previously optimized targeting profile.When nanoparticles (NPs) enter a biological environment, proteins bind to their surface forming a protein coating, which alters NP features giving it a biological identity, which controls its physiological response. The NP biological identity (size, charge and aggregation state) does strictly correlate with its physicochemical properties and the nature of the biological environment. While the former relationship has been extensively investigated, whether and how alterations in the physiological environment affect the biological identity of the NPs remains unclear. In this work we enrolled healthy and histologically proven pancreatic cancer patients. A statistically significant reduction in the level of clinically relevant proteins in cancer patients occurred. Positively and negatively charged lipid nanoparticles with two different surface chemistries (plain and PEGylated) were incubated with human plasma from both groups and characterized thoroughly by dynamic light scattering and zet
Environmental impact of co-combustion of polyethylene wastes in a rice husks fueled plant: evaluation of organic micropollutants and PM emissions
No full textCo-combustion of biomass and plastic waste has emerged as one of the most promising approach at the plastic waste management challenge. This strategy is particularly attractive since it can simultaneously solve the increasing energy demand and reduce the plastic wastes volume. However, since the combustion of both plastic wastes and natural materials is a potential source of organic micropollutants, such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), polychlorinated biphenyls (PCBs) and of polycyclic aromatic hydrocarbons (PAHs), beside particulate matter, the environmental sustainability of the waste to energy (WtE) co-combustion strategy has to be assessed. To this end, the emissions of dioxin like (dl)-PCBs, PCDD/Fs and PAHs from a 4-MW thermal power plant fueled with rice husk, partially replaced by end-of-life polyethylene (PE) industrial waste (up to 15% of the thermal power of the plant), were investigated. GC-MS/MS analyses have demonstrated that the co-combustion of PE waste and rice husk presents a profile of environmental sustainability. The concentrations of dl-PCBs, PCDD/Fs and PAHs were extremely low and they have remained almost unaffected by introducing PE in feed. In particular, emissions of PCCD/Fs and dl-PCBs in flue gas were in the range 0.6-1.0 and 0.2-0.6 pg TEQ/Nm3, respectively, while PAHs concentrations ranged from 410 to 825 ng/Nm3. Furthermore, the emission factors of these organic pollutants were found to be lower with PE increasing rate while particulate matter emissions were not affected by co-combustions. Collectively, the investigation has demonstrated that the noils of the industrial PE, due to the low content in halides and metals, can be used as auxiliary fuel and energetically recycled through co-combustion with rice husk. This case of study represents an effective application of the WtE strategy and a concrete approach to mitigate the threat of plastic pollution
Structural characterization of cationic liposome/poly(I:C) complexes showing high ability in eliminating prostate cancer cells
No full textPolyriboinosinic acid-polyribocytidylic acid (poly(I:C)) is a mimic of viral double-strand (ds) RNA that induces apoptosis in many cancer cells. However, toxicity and stability issues so far prevented its application as it undergoes enzymatic degradation and bear the potential to trigger undue immune stimulation as well as autoimmune disorders. Encapsulation of antitumor drugs is frequently used to improve their effectiveness by lowering the necessary dosage. In this study we examined the ability of cationic liposomes to deliver poly(I:C) into PC3 and DU145 cell lines, derived from human bone and brain prostate cancer metastasis, respectively. The first formulation was made of the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the zwitterionic lipid dioleoylphosphocholine (DOPC). The second one was the binary lipid system made of the cationic 3 beta-[N-(N',N'-dimethylaminoethane)-carbamoyl]-cholesterol (DC-Chol) and the zwitterionic helper lipid dioleoylphosphatidylethanolamine (DOPE), while the third formulation was the multicomponent (MC) lipid system encapsulating the four lipid species simultaneously. Synchrotron small angle X-ray scattering revealed that cationic liposome/poly(I:C) complexes exhibit lamellar phases structurally similar to cationic liposome/DNA complexes. We further found that cationic liposomes/poly(I:C) complexes were up to 10 times more efficient in eliminating metastatic prostate cancer cells than the free drug. Finally, the ability of distinct lipid formulations to induce apoptosis could inversely correlate with their endosomal escape ability. This property of cationic liposome/poly(I:C) complexes contrasts to cationic liposome/DNA complexes, where the endosomal escape ability is the rate-limiting step for the transfection efficiency
Analytical strategies based on chromatography-mass spectrometry for the determination of estrogen-mimicking compounds in food
No full textFood safety can be compromised by the presence of a wide variety of substances, deriving from both natural and anthropogenic sources. Among these substances, compounds exhibiting various degrees of estrogenic activity have been widely studied in environmental samples, whereas less attention has been devoted to food matrices. The aim of the present review is to give a general overview on the recent analytical methods based on gas or liquid chromatography coupled to mass spectrometry for the determination of estrogen-like compounds in foods, including new developments, improvements and upcoming trends in the field. Attention will be focused on four representative groups of compounds, i.e. natural and synthetic estrogens, mycoestrogens, phytoestrogens, and alkylphenols. (c) 2013 Elsevier B.V. All rights reserved
Membrane proteome functional characterization of breast cancer-initiating cells subjected to bone morphogenetic protein signaling inhibition by dorsomorphin
No full textIn this study, A17 cells, which are an invasive mesenchymal cell line with cancer stem cell properties, were exploited for the study of the role of bone morphogenetic protein pathways in cancer-initiating cells employing a proteomics-based approach. A17 cells were treated with the bone morphogenetic protein signaling inhibitor dorsomorphin for 3 days. After that, subcellular fractionation of cell samples was performed and the membrane fraction analyzed by shotgun proteomics. The extracted membrane proteins were enzymatically digested and the resulting peptide mixture was analyzed by nano liquid chromatography coupled to tandem mass spectrometry and relative label-free quantitation. Protein profiles of A17 membrane fractions before and after dorsomorphin treatment were compared, and further mined by Gene Ontology search. The protein profile of untreated A17 samples correlated with the mesenchymal phenotype, whereas changes were observed in dorsomorphin-treated samples, further supporting a mesenchymal to epithelial transition upon bone morphogenetic protein signaling pathway inhibition and the importance of this pathway in breast cancer cell malignancy
Evaluation of the concentration of the toxic 2,3,6,7-tetrachlorobiphenylene in air after an electrical material fire
No full textIt is known that when fires or explosions involve electrical systems, along with PCDDs and PCDFs, polychlorinated biphenylenes (PCBPs) are also produced. These chlorinated tricyclic aromatic pollutants were noticed in fire rubbles and after the World Trade Center destruction. However, the analytical difficulties in developing an efficient method have limited the knowledge of their environmental distribution. In light of the equipotency of 2,3,6,7-TeCBP and 2,3,7,8-TeCDD, PCBPs call for more accurate investigations. In this paper, for the first time, the level and persistence of 2,3,6,7-TeCBP have been investigated in air samples (both indoor and outdoor) after a fire broke out in an industrial building. GC–MS/MS analysis revealed that 2,3,6,7-TeCBP concentrations after the fire (3046 fg/m3 at the “epicentre”) were remarkably higher than that of the 2,3,7,8-TeCDD. Moreover, the monitoring for over two years has demonstrated the persistent nature of this compound. 2,3,6,7-TeCBP was also analyzed in two different ambient air scenario: industrial and periurban areas and in both cases its concentrations were no matter of concern, confirming the correlation of 2,3,6,7-TeCBP with fire episodes. Collectively, 2,3,6,7-TeCBP, because of its toxicity, concentration and persistence, is a crucial compound in the evaluation of the health effects correlated with fires of electrical systems
Analytical Methods for Characterizing the Nanoparticle-Protein Corona
No full textWhen nanoparticles (NPs) enter a biological environment, medium components, especially proteins, compete for binding to the NP's surface, leading to development of a new interface, commonly referred to as the "protein corona." This rich protein shell gives the NPs a biological identity that can be very different from their synthetic one, in terms of their chemical-physical properties. Understanding NP-protein interaction is crucial for both the bioapplications and safety of nanomaterials. The protein corona provides the primary contact to the cells and their receptors. It defines in vivo fate of the delivery systems, governing the stability, immunogenicity, circulation, clearance rates and organ biodistribution of the NPs. Given its importance, the application and the development of analytical methods to investigate the protein corona are crucial. This review gives an overview of chromatographic, electrophoretic, mass spectrometric and proteomic methods because these techniques have the advantage to be able to identify and quantify individual proteins adsorbed onto the corona. This capability opens up the possibility to exploit the protein corona for specific cell targeting. © 2014 Springer-Verlag
Killing cancer cells using nanotechnology: novel poly(I:C) loaded liposome-silica hybrid nanoparticles
No full textPolyinosinic-polycytidylic acid (poly(I:C)) is a synthetic double-stranded RNA (dsRNA) analog able to induce apoptosis in different cancer cells by the activation of toll-like receptor 3 (TLR3) and cytosolic helicases, retinoic acid inducible gene I (RIG-I) like receptors. In this work, we have synthesized and thoroughly characterized a core-shell liposome-silica hybrid (LSH) nanoparticle (NP) made of a silica core surrounded by a multicomponent cationic lipid bilayer. In view of in vivo applications, a variant with polyethyleneglycol (PEG) grafted onto the lipid surface was also synthesized. Poly(I:C)-loaded LSH NPs were characterized and optimized in terms of their chemical-physical properties by using dynamic light scattering (DLS), micro-electrophoresis and transmission electron microscopy (TEM). The ability of this new technology to kill cancer cells was validated in PC3 prostate cancer and MCF7 breast cancer cells by MTT proliferation assay, flow cytometry and fluorescence confocal microscopy. We found that negatively charged poly(I:C)-loaded LSH NPs are more efficient than their liposome counterpart in eliminating cancer cells, thus representing excellent candidates for both in vitro and in vivo drug delivery applications
A proteomics-based methodology to investigate the protein corona effect for targeted drug delivery.
No full textHere we introduce a proteomics methodology based on nanoliquid-chromatography tandem mass spectrometry (nanoLC/MS-MS) to investigate the "protein corona effect for targeted drug delivery", an innovative strategy, which exploits the "protein corona" that forms around nanoparticles in a physiological environment to target cells
The protein corona of circulating PEGylated liposomes
No full textFollowing systemic administration, liposomes are covered by a ‘corona’ of proteins, and preserving the surface functionality is challenging. Coating the liposome surface with polyethylene glycol (PEG) is the most widely
used anti-opsonization strategy, but it cannot fully preclude protein adsorption. To date, protein binding has been studied following in vitro incubation to predict the fate of liposomes in vivo, while dynamic incubation mimicking in vivo conditions remains largely unexplored. The main aim of this investigation was to determine whether shear stress, produced by physiologically relevant dynamic flow, could influence the liposomeprotein corona. The corona of circulating PEGylated liposome was thoroughly compared with that formed by incubation in vitro. Systematic comparison in terms of size, surface charge and quantitative composition was made by dynamic light scattering, microelectrophoresis and nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS). Size of coronas formed under static vs. dynamic incubation did not appreciably differ from each other. On the other side, the corona of circulating liposomes was more negatively charged than its static counterpart. Of note, the variety of protein species in the corona formed in a dynamic flow was significantly wider. Collectively, these results demonstrated that the corona of circulating PEGylated liposomes can be considerably different from that formed in a static fluid. This seems to be a key factor to predict the biological activity of a liposomal formulation in a physiological environment
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