RESUMO
The rapid development of nanotechnology has greatly benefited modern science and engineering and also led to an increased environmental exposure to nanoparticles (NPs). While recent research has established a correlation between the exposure of NPs and cardiovascular diseases, the intrinsic mechanisms of such a connection remain unclear. Inhaled NPs can penetrate the air-blood barrier from the lung to systemic circulation, thereby intruding the cardiovascular system and generating cardiotoxic effects. In this study, on-site cardiovascular damage was observed in mice upon respiratory exposure of silica nanoparticles (SiNPs), and the corresponding mechanism was investigated by focusing on the interaction of SiNPs and their encountered biomacromolecules en route. SiNPs were found to collect a significant amount of apolipoprotein A-I (Apo A-I) from the blood, in particular when the SiNPs were preadsorbed with pulmonary surfactants. While the adsorbed Apo A-I ameliorated the cytotoxic and proinflammatory effects of SiNPs, the protein was eliminated from the blood upon clearance of the NPs. However, supplementation of Apo A-I mimic peptide mitigated the atherosclerotic lesion induced by SiNPs. In addition, we found a further declined plasma Apo A-I level in clinical silicosis patients than coronary heart disease patients, suggesting clearance of SiNPs sequestered Apo A-I to compromise the coronal protein's regular biological functions. Together, this study has provided evidence that the protein corona of SiNPs acquired in the blood depletes Apo A-I, a biomarker for prediction of cardiovascular diseases, which gives rise to unexpected toxic effects of the nanoparticles.
Assuntos
Apolipoproteína A-I/deficiência , Doenças Cardiovasculares/etiologia , Nanopartículas/efeitos adversos , Adsorção/efeitos dos fármacos , Animais , Apolipoproteína A-I/sangue , Sistema Cardiovascular , Pulmão , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nanopartículas/química , Nanotecnologia , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Transdução de Sinais/efeitos dos fármacos , Dióxido de Silício/efeitos adversos , Dióxido de Silício/químicaRESUMO
Nanotoxicology and nanomedicine are two sub-disciplines of nanotechnology focusing on the phenomena, mechanisms, and engineering at the nano-bio interface. For the better part of the past three decades, these two disciplines have been largely developing independently of each other. Yet recent breakthroughs in microbiome research and the current COVID-19 pandemic demonstrate that holistic approaches are crucial for solving grand challenges in global health. Here we show the Yin and Yang relationship between the two fields by highlighting their shared goals of making safer nanomaterials, improved cellular and organism models, as well as advanced methodologies. We focus on the transferable knowledge between the two fields as nanotoxicological research is moving from pristine to functional nanomaterials, while inorganic nanomaterials - the main subjects of nanotoxicology - have become an emerging source for the development of nanomedicines. We call for a close partnership between the two fields in the new decade, to harness the full potential of nanotechnology for benefiting human health and environmental safety.
RESUMO
Amyloid fibrils generally display chirality, a feature which has rarely been exploited in the development of therapeutics against amyloid diseases. This study reports, for the first time, the use of mesoscopic chiral silica nanoribbons against the in vivo amyloidogenesis of human islet amyloid polypeptide (IAPP), the peptide whose aggregation is implicated in type 2 diabetes. The thioflavin T assay and transmission electron microscopy show accelerated IAPP fibrillization through elimination of the nucleation phase and shortening of the elongation phase by the nanostructures. Coarse-grained simulations offer complementary molecular insights into the acceleration of amyloid aggregation through their nonspecific binding and directional seeding with the nanostructures. This accelerated IAPP fibrillization translates to reduced toxicity, especially for the right-handed silica nanoribbons, as revealed by cell viability, helium ion microscopy, as well as zebrafish embryo survival, developmental, and behavioral assays. This study has implicated the potential of employing chiral nanotechnologies against the mesoscopic enantioselectivity of amyloid proteins and their associated diseases.
Assuntos
Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Nanotubos de Carbono/química , Dióxido de Silício/química , Humanos , EstereoisomerismoRESUMO
The potential applications of nanomaterials as drug delivery systems and in other products continue to expand. Upon introduction into physiological environments and driven by energetics, nanomaterials readily associate proteins forming a protein corona (PC) on their surface. This PC influences the nanomaterial's surface characteristics and may impact their interaction with cells. To determine the biological impact of nanomaterial exposure as well as nanotherapeutic applications, it is necessary to understand PC formation. Utilizing a label-free mass spectrometry-based proteomics approach, we examined the composition of the PC for a set of four silver nanoparticles (AgNPs) including citrate-stabilized and polyvinlypyrrolidone-stabilized (PVP) colloidal silver (20 or 110 nm diameter). To simulate cell culture conditions, AgNPs were incubated for 1 h in Dulbecco's Modified Eagle Medium supplemented with 10% fetal bovine serum, washed, coronal proteins solubilized, and proteins identified and quantified by label-free LC-MS/MS. To determine which attributes influence PC formation, the AgNPs were characterized in both water and cell culture media with 10% FBS. All AgNPs associated a common subset of 11 proteins including albumin, apolipoproteins, keratins, and other serum proteins. 110 nm citrate- and PVP-stabilized AgNPs were found to bind the greatest number of proteins (79 and 85 respectively) compared to 20 nm citrate- and PVP-stabilized AgNPs (45 and 48 respectively), suggesting a difference in PC formation based on surface curvature. While no relationships were found for other protein parameters (isoelectric point or aliphatic index), the PC on 20 nm AgNPs (PVP and citrate) consisted of more hydrophobic proteins compared to 110 nm AgNPs implying that this class of proteins are more receptive to curvature-induced folding and crowding in exchange for an increased hydration in the aqueous environment. These observations demonstrate the significance of electrostatic and hydrophobic interactions in the formation of the PC which may have broad biological and toxicological implications.
Assuntos
Meios de Cultura/química , Nanopartículas Metálicas/química , Proteínas/química , Prata/química , Animais , Proteínas de Transporte/química , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas Metálicas/ultraestrutura , Tamanho da Partícula , Ligação Proteica , ProteômicaRESUMO
The vast use of silver nanoparticles (AgNPs) mandates thorough investigation of their impact on biosystems at various levels. The cytotoxicity of PVP coated-AgNPs to pollen, the aploid male gametophyte of higher plants, has been assessed here for the first time. The negative effects of AgNPs include substantial decreases in pollen viability and performance, specific ultrastructural alterations, early changes in calcium content, and unbalance of redox status. Ag⺠released from AgNPs damaged pollen membranes and inhibited germination to a greater extent than the AgNPs themselves. By contrast, the AgNPs were more potent at disrupting the tube elongation process. ROS deficiency and overproduction were registered in the Agâº- and AgNP-treatment, respectively. The peculiar features of AgNP toxicity reflected their specific modes of interaction with pollen surface and membranes, and the dynamic exchange between coating (PVP) and culture medium. In contrast, the effects of Ag⺠were most likely induced through chemical/physicochemical interactions.
Assuntos
Actinidia/efeitos dos fármacos , Germinação/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Pólen/efeitos dos fármacos , Prata/toxicidade , Actinidia/fisiologia , Nanopartículas Metálicas/química , Pólen/fisiologia , Prata/químicaRESUMO
BACKGROUND: Recent research on nanoparticles in a number of crops has evidenced for enhanced germination and seedling growth, physiological activities including photosynthetic activity and nitrogen metabolism, mRNA expression and protein level, and also positive changes in gene expression indicating their potential use in crop improvement. We used a medicinally rich vegetable crop, bitter melon, as a model to evaluate the effects of seed treatment with a carbon-based nanoparticle, fullerol [C60(OH)20], on yield of plant biomass and fruit characters, and phytomedicine contents in fruits. RESULTS: We confirmed the uptake, translocation and accumulation of fullerol through bright field imaging and Fourier transform infra-red spectroscopy. We observed varied effects of seed treatment at five concentrations, including non-consequential and positive, on plant biomass yield, fruit yield and its component characters, and content of five phytomedicines in fruits. Fullerol-treatment resulted in increases up to 54% in biomass yield and 24% in water content. Increases of up to 20% in fruit length, 59% in fruit number, and 70% in fruit weight led to an improvement up to 128% in fruit yield. Contents of two anticancer phytomedicines, cucurbitacin-B and lycopene, were enhanced up to 74% and 82%, respectively, and contents of two antidiabetic phytomedicines, charantin and insulin, were augmented up to 20% and 91%, respectively. Non-significant correlation inter se plant biomass, fruit yield, phytomedicine content and water content evidenced for separate genetic control and biosynthetic pathways for production of plant biomass, fruits, and phytomedicines in fruits, and also no impact of increased water uptake. CONCLUSIONS: While our results indicated possibility of improving crop yield and quality by using proper concentrations of fullerol, extreme caution needs to be exercised given emerging knowledge about accumulation and toxicity of nanoparticles in bodily tissues.
Assuntos
Biomassa , Fulerenos/química , Momordica charantia/crescimento & desenvolvimento , Nanotecnologia , Carotenoides/biossíntese , Frutas/química , Frutas/metabolismo , Fulerenos/metabolismo , Fulerenos/farmacologia , Germinação/efeitos dos fármacos , Glucosídeos/biossíntese , Insulina/genética , Insulina/metabolismo , Licopeno , Momordica charantia/metabolismo , Plântula/efeitos dos fármacos , Plântula/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Distribuição Tecidual , Triterpenos/metabolismo , Água/metabolismoRESUMO
As nanotechnology rapidly emerges into a new industry-driven by its enormous potential to revolutionize electronics, materials, and medicine-exposure of living species to discharged nanoparticles has become inevitable. Despite the increased effort on elucidating the environmental impact of nanotechnology, literature on higher plants exposure to nanoparticles remains scarce and often contradictory. Here we present our biophysical methodologies for the study of carbon nanoparticle uptake by Allium cepa cells and rice plants. We address the three essential aspects for such studies: identification of carbon nanoparticles in the plant species, quantification of nanotransport and aggregation in the plant compartments, and evaluation of plant responses to nanoparticle exposure on the cellular and organism level. Considering the close connection between plant and mammalian species in ecological systems especially in the food chain, we draw a direct comparison on the uptake of carbon nanoparticles in plant and mammalian cells. In addition to the above studies, we present methods for assessing the effects of quantum dot adsorption on algal photosynthesis.