Human Lung A549 Cells Research Articles

A Lipidated Peptide with Mitochondrial Membrane Localization in Human A549 Lung Cells: From Enhanced Cell-Penetrating Properties to Biological Activity Mechanism.

Here, a lipidated peptide Pal-pHK-pKV with self-assembly properties and the ability to provoke the disruption of the mitochondrial voltage-dependent anion channel-1 protein (VDAC1)-hexokinase-II (HK-II) complex is reported. The effects of the peptide pHK (N-terminal 15-amino acid fragment of HK-II that specifically binds VDAC1) are compared to those of a designed biomimetic amphiphilic pHK-pKV conjugate (pHK coupled with a cell-penetrating peptide pKV) and Pal-pHK-pKV (a lipidated conjugate modified with a hydrophobic palmitic (Pal) alkyl chain). The Pal-pHK-pKV exhibits a stronger interaction with the membrane as compared to pHK-pKV, which is demonstrated by the Langmuir-Blodgett technique and two-photon excitation microscopy. The amphiphilic peptide derivatives are cytotoxic to the A549 cells, but Pal-pHK-pKV is more cytotoxic. The inhibitory effects of the pHK derivatives on the A549 cells growth are investigated through induced apoptosis pathway, depolarized mitochondrial membrane potential, inhibited glycolysis, and activated caspase. The results of the immunofluorescence evidence the specific mitochondrial targeting by those derivatives.

Selective Inhibition of the Interaction between SARS-CoV-2 Spike S1 and ACE2 by SPIDAR Peptide Induces Anti-Inflammatory Therapeutic Responses.

Many patients with coronavirus disease 2019 in intensive care units suffer from cytokine storm. Although anti-inflammatory therapies are available to treat the problem, very often, these treatments cause immunosuppression. Because angiotensin-converting enzyme 2 (ACE2) on host cells serves as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), to delineate a SARS-CoV-2-specific anti-inflammatory molecule, we designed a hexapeptide corresponding to the spike S1-interacting domain of ACE2 receptor (SPIDAR) that inhibited the expression of proinflammatory molecules in human A549 lung cells induced by pseudotyped SARS-CoV-2, but not vesicular stomatitis virus. Accordingly, wild-type (wt), but not mutated (m), SPIDAR inhibited SARS-CoV-2 spike S1-induced activation of NF-κB and expression of IL-6 and IL-1β in human lung cells. However, wtSPIDAR remained unable to reduce activation of NF-κB and expression of proinflammatory molecules in lungs cells induced by TNF-α, HIV-1 Tat, and viral dsRNA mimic polyinosinic-polycytidylic acid, indicating the specificity of the effect. The wtSPIDAR, but not mutated SPIDAR, also hindered the association between ACE2 and spike S1 of SARS-CoV-2 and inhibited the entry of pseudotyped SARS-CoV-2, but not vesicular stomatitis virus, into human ACE2-expressing human embryonic kidney 293 cells. Moreover, intranasal treatment with wtSPIDAR, but not mutated SPIDAR, inhibited lung activation of NF-κB, protected lungs, reduced fever, improved heart function, and enhanced locomotor activities in SARS-CoV-2 spike S1-intoxicated mice. Therefore, selective targeting of SARS-CoV-2 spike S1-to-ACE2 interaction by wtSPIDAR may be beneficial for coronavirus disease 2019.

Bioinformatics analyses reveal cell-barrier junction modulations in lung epithelial cells on SARS-CoV-2 infection

ABSTRACT Cell junctions maintain the blood-tissue barriers to preserve vascular and tissue integrity. Viral infections reportedly modulate cell–cell junctions to facilitate their invasion. However, information on the effect of COVID-19 infection on the gene expression of cell junction and cytoskeletal proteins is limited. Using the Gene Expression Omnibus and Reactome databases, we analyzed the data on human lung A549, NHBE, and Calu-3 cells for the expression changes in cell junction and cytoskeletal proteins by SARS-CoV-2 (CoV-2) infection. The analysis revealed changes in 3,660 genes in A549, 100 genes in NHBE, and 592 genes in Calu-3 cells with CoV-2 infection. Interestingly, EGOT (9.8-, 3- and 8.3-fold; p < .05) and CSF3 (4.3-, 33- and 56.3-fold; p < .05) were the only two genes significantly elevated in all three cell lines (A549, NHBE and Calu-3, respectively). On the other hand, 39 genes related to cell junctions and cytoskeleton were modulated in lung cells, with DLL1 demonstrating alterations in all cells. Alterations were also seen in several miRNAs associated with the cell junction and cytoskeleton genes modulated in the analysis. Further, matrix metalloproteinases involved in disease pathologies, including MMP-3, -9, and -12 demonstrated elevated expression on CoV-2 infection (p < .05). The study findings emphasize the integral role of cell junction and cytoskeletal genes in COVID-19, suggesting their therapeutic potential. Our analysis also identified a distinct EGOT gene that has not been previously implicated in COVID-19. Further studies on these newly identified genes and miRNAs could lead to advances in the pathogenesis and therapeutics of COVID-19.

Eugenol, a Component of Holy Basil (Tulsi) and Common Spice Clove, Inhibits the Interaction Between SARS-CoV-2 Spike S1 and ACE2 to Induce Therapeutic Responses.

Spike S1 of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) on host cells to enter the cell and initiate COVID-19. Since ACE2 is a favorable enzyme, we were interested in finding a molecule capable of binding spike S1, but not ACE2, and inhibiting the interaction between spike S1 and ACE2. Holy basil (Tulsi) has a long history as a medicine for different human disorders. Therefore, we screened different components of Tulsi leaf and found that eugenol, but not other major components (e.g. ursolic acid, oleanolic acid and β-caryophylline), inhibited the interaction between spike S1 and ACE2 in an AlphaScreen-based assay. By in silico analysis and thermal shift assay, we also observed that eugenol associated with spike S1, but not ACE2. Accordingly, eugenol strongly suppressed the entry of pseudotyped SARS-CoV-2, but not vesicular stomatitis virus (VSV), into human ACE2-expressing HEK293 cells. Eugenol also reduced SARS-CoV-2 spike S1-induced activation of NF-κB and the expression of IL-6, IL-1β and TNFα in human A549 lung cells. Moreover, oral treatment with eugenol reduced lung inflammation, decreased fever, improved heart function, and enhanced locomotor activities in SARS-CoV-2 spike S1-intoxicated mice. Therefore, selective targeting of SARS-CoV-2 spike S1, but not ACE2, by eugenol may be beneficial for COVID-19 treatment.Graphic

Bioscaffold Stiffness Mediates Aerosolized Nanoparticle Uptake in Lung Epithelial Cells.

In this study, highly porous, ultrasoft polymeric mats mimicking human tissues were formed from novel polyurethane soft dendritic colloids (PU SDCs). PU SDCs have a unique fibrillar morphology controlled by antisolvent precipitation. When filtered from suspension, PU SDCs form mechanically robust nonwoven mats. The stiffness of the SDC mats can be tuned for physiological relevance. The unique physiochemical characteristics of the PU SDC particles dictate the mechanical properties resulting in tunable elastic moduli ranging from 200 to 800 kPa. The human lung A549 cells cultured on both stiff and soft PU SDC membranes were found to be viable, capable of supporting the air-liquid interface (ALI) cell culture, and maintained barrier integrity. Furthermore, A549 cellular viability and uptake efficiency of aerosolized tannic acid-coated gold nanoparticles (Ta-Au) was found to depend on elastic modulus and culture conditions. Ta-Au nanoparticle uptake was twofold and fourfold greater on soft PU SDCs, when cultured at submerged and ALI conditions, respectively. The significant increase in endocytosed Ta-Au resulted in a 20% decrease in viability, and a 4-fold increase in IL-8 cytokine secretion when cultured on soft PU SDCs at ALI. Common tissue culture materials exhibit super-physiological elastic moduli, a factor found to be critical in analyzing nanomaterial cellular interactions and biological responses.

Cytotoxicity and estrogenicity in simulated dental wastewater after grinding of resin-based materials

ObjectiveThis study evaluated the cytotoxic and estrogenic effects of dust and eluates released into simulated wastewater after grinding of dental resin-based materials. MethodsFour materials were used: ceram.x® universal, Filtek™ Supreme XTE, Lava™ Ultimate and Core-X™ flow. From each composite material, samples (5 × 2 mm, n = 50) were prepared according to the manufacturers’ instructions. Lava™ Ultimate was used as blocks. All samples were ground to dust with a diamond bur (106 μm) and suspended in distilled water at 60 mg/mL. After storage for 72 h, the suspensions were separated into a soluble (eluate) and a particulate (dust) fraction. Eluates and dusts were evaluated for inhibition of Vibrio fischeri bioluminescence and cytotoxicity on human A549 lung cells (WST-1-Assay). The estrogenic activity was assessed by YES-Assay using Saccharomyces cerevisiae. Additionally, dental monomers (BisGMA, BisEMA, UDMA, TEGDMA, HEMA) and Bisphenol A were investigated. ResultsAll eluates showed inhibition of V. fischeri bioluminescence at concentrations above 1.1 mg/mL (p < 0.05). The activity of the eluates of ceram.x® universal and Filtek™ Supreme XTE was significantly higher than Lava™ Ultimate and Core-X™ flow (p < 0.05). In the WST-1-Assay, all materials induced cytotoxic effects at concentrations of 0.1 mg/mL (p < 0.05), while no significant differences were detected among them. The tested materials revealed no estrogenic activity. All dental monomers and Bisphenol A showed concentration dependent cytotoxic effects (p < 0.05), whereas only Bisphenol A induced an estrogenic effect (p < 0.01). SignificanceDust and eluates of resin-based dental materials released into wastewater exert bactericidal and cytotoxic effects in vitro. However, they reveal no estrogenic effect.

RuvB-Like Protein 2 Interacts with the NS1 Protein of Influenza A Virus and Affects Apoptosis That Is Counterbalanced by Type I Interferons.

The NS1 protein of influenza A virus (IAV) plays important roles in viral pathogenesis and host immune response. Through a proteomic approach, we have identified RuvB-like proteins 1 and 2 (RuvBL1 and RuvBL2) as interacting partners of the NS1 protein of IAVs. Infection of human lung A549 cells with A/PR/8/34 (PR8) virus resulted in reductions in the protein levels of RuvBL2 but not RuvBL1. Further studies with RuvBL2 demonstrated that the NS1-RuvBL2 interaction is RNA-independent, and RuvBL2 binds the RNA-binding domain of the NS1. Infection of interferon (IFN)-deficient Vero cells with wild-type or delNS1 PR8 virus reduced RuvBL2 protein levels and induced apoptosis; delNS1 virus caused more reductions in RuvBL2 protein levels and induced more apoptosis than did wild-type virus. Knockdown of RuvBL2 by siRNAs induced apoptosis and overexpression of RuvBL2 resulted in increased resistance to infection-induced apoptosis in Vero cells. These results suggest that a non-NS1 viral element or elements induce apoptosis by suppressing RuvBL2 protein levels, and the NS1 inhibits the non-NS1 viral element-induced apoptosis by maintaining RuvBL2 abundance in infected cells in the absence of IFN influence. In contrast to Vero cells, infection of IFN-competent A549 cells with PR8 virus caused reductions in RuvBL2 protein levels but did not induce apoptosis. Concomitantly, pretreatment of Vero cells with a recombinant IFN resulted in resistance to infection-induced apoptosis. These results demonstrate that the infection-induced, RuvBL2-regulated apoptosis in infected cells is counterbalanced by IFN survival signals. Our results reveal a novel mechanism underlying the infection-induced apoptosis that can be modulated by the NS1 and type I IFN signaling in IAV-infected cells.

Relationship between Cytotoxicity and Surface Oxidation of Artificial Black Carbon.

The lacking of laboratory black carbon (BC) samples have long challenged the corresponding toxicological research; furthermore, the toxicity tests of engineered carbon nanoparticles were unable to reflect atmospheric BC. As a simplified approach, we have synthesized artificial BC (aBC) for the purpose of representing atmospheric BC. Surface chemical properties of aBC were controlled by thermal treatment, without transforming its physical characteristics; thus, we were able to examine the toxicological effects on A549 human lung cells arising from aBC with varying oxidation surface properties. X-ray photoelectron spectroscopy, as well as Raman and Fourier transform infrared spectroscopy, verified the presence of increased amounts of oxygenated functional groups on the surface of thermally-treated aBC, indicating aBC oxidization at elevated temperatures; aBC with increased oxygen functional group content displayed increased toxicity to A549 cells, specifically by decreasing cell viability to 45% and elevating reactive oxygen species levels up to 294% for samples treated at 800 °C.

Interactive toxicity effect of combined exposure to hematite and amorphous silicon dioxide nanoparticles in human A549 cell line.

The study on the health effects of combined exposure to various contaminants has been recommended by many authors. The objective of the present study was to examine the effects of the co-exposure to hematite and amorphous silicon dioxide (A-SiO2) nanoparticles on the human lung A549 cell line. The A549 cell line was exposed to 10, 50, 100, and 250 µg/ml concentrations of hematite and A-SiO2 nanoparticles both independently and in combination. Their toxicity in both circumstances was investigated by MTT, intracellular reactive oxygen species, cell glutathione content, and mitochondrial membrane potential tests, and the type of interaction was investigated by statistical analysis using Statistical Package for Social Sciences (SPSS, v. 21). Results showed that the independent exposure to either hematite or A-SiO2 compared with the control group produced more toxic effects on the A549 cell line. The toxicity of combined exposure of the nanoparticles was lower compared with independent exposure, and antagonistic interactive effects were detected. The findings of this study could be useful in clarifying the present debate on the health effects of combined exposure of hematite and A-SiO2 nanoparticles. Because of the complexities of combined exposures, further studies of this kind are recommended.

An autoantigen profile of human A549 lung cells reveals viral and host etiologic molecular attributes of autoimmunity in COVID-19

We aim to establish a comprehensive COVID-19 autoantigen atlas in order to understand autoimmune diseases caused by SARS-CoV-2 infection. Based on the unique affinity between dermatan sulfate and autoantigens, we identified 348 proteins from human lung A549 cells, of which 198 are known targets of autoantibodies. Comparison with current COVID data identified 291 proteins that are altered at protein or transcript level in SARS-CoV-2 infection, with 191 being known autoantigens. These known and putative autoantigens are significantly associated with viral replication and trafficking processes, including gene expression, ribonucleoprotein biogenesis, mRNA metabolism, translation, vesicle and vesicle-mediated transport, and apoptosis. They are also associated with cytoskeleton, platelet degranulation, IL-12 signaling, and smooth muscle contraction. Host proteins that interact with and that are perturbed by viral proteins are a major source of autoantigens. Orf3 induces the largest number of protein alterations, Orf9 affects the mitochondrial ribosome, and they and E, M, N, and Nsp proteins affect protein localization to membrane, immune responses, and apoptosis. Phosphorylation and ubiquitination alterations by viral infection define major molecular changes in autoantigen origination. This study provides a large list of autoantigens as well as new targets for future investigation, e.g., UBA1, UCHL1, USP7, CDK11A, PRKDC, PLD3, PSAT1, RAB1A, SLC2A1, platelet activating factor acetylhydrolase, and mitochondrial ribosomal proteins. This study illustrates how viral infection can modify host cellular proteins extensively, yield diverse autoantigens, and trigger a myriad of autoimmune sequelae. Our work provides a rich resource for studies into “long COVID” and related autoimmune sequelae.

Avermectin induced DNA damage to the apoptosis and autophagy in human lung epithelial A549 cells

Avermectin (AVM), as a biological insecticide, is widely used in agriculture and forestry production globally. However, inhalation of AVM may pose a risk, and the lung is the direct target, but the cytotoxicity of AVM on human lung cells is still unclear. Here, we attempted to elucidate the cytotoxic effect and molecular mechanism of AVM on human lung A549 cells. The results indicated that AVM inhibits cell proliferation, and enhances programmed cell death (apoptosis and autophagy). In addition, we found the AVM-treated cells showed an obvious drop in mitochondrial membrane potential and LC3-I/II, increased ROS production, DNA double-strand breaks, caspase-3/9 activated, PARP cleaved, cytochrome c and Bax/Bcl-2 content rise. The results showed that AVM induced mitochondria-related apoptosis and autophagy in lung A549 cells. These results indicate that AVM can pose a potential threat to human health by inducing DNA damage and programmed cell death.

Polyphosphate Reverses the Toxicity of the Quasi-Enzyme Bleomycin on Alveolar Endothelial Lung Cells In Vitro.

Simple SummaryBleomycin (BLM) is a medication introduced used to treat various types of cancer, including testicular cancer, ovarian cancer, and Hodgkin’s disease. Its most serious side effect is pulmonary fibrosis and impaired lung function. Using A549 human lung cells it is shown that, in parallel to an increased cell toxicity and DNA damage, BLM causes a marked enlargement of the cell nucleus. This effect is abolished by inorganic polyphosphate (polyP), if this physiological polymer is administered together with BLM. The detoxification of BLM is–most likely–caused by the upregulation of the gene encoding the BLM hydrolase which inactivates BLM in vitro and in vivo. This study contributes also to a rational application in COVID-19 patients since polyP prevents binding of SARS-CoV-2 to host cells.The anti-cancer antitumor antibiotic bleomycin(s) (BLM) induces athyminic sites in DNA after its activation, a process that results in strand splitting. Here, using A549 human lung cells or BEAS-2B cells lunc cells, we show that the cell toxicity of BLM can be suppressed by addition of inorganic polyphosphate (polyP), a physiological polymer that accumulates and is released from platelets. BLM at a concentration of 20 µg ml−1 causes a decrease in cell viability (by ~70%), accompanied by an increased DNA damage and chromatin expansion (by amazingly 6-fold). Importantly, the BLM-caused effects on cell growth and DNA integrity are substantially suppressed by polyP. In parallel, the enlargement of the nuclei/chromatin in BLM-treated cells (diameter, 20–25 µm) is normalized to ~12 µm after co-incubation of the cells with BLM and polyP. A sequential application of the drugs (BLM for 3 days, followed by an exposure to polyP) does not cause this normalization. During co-incubation of BLM with polyP the gene for the BLM hydrolase is upregulated. It is concluded that by upregulating this enzyme polyP prevents the toxic side effects of BLM. These data might also contribute to an application of BLM in COVID-19 patients, since polyP inhibits binding of SARS-CoV-2 to cellular ACE2.

Combustion-derived particles from biomass sources differently promote epithelial-to-mesenchymal transition on A549 cells

Combustion-derived particles (CDPs), due to the presence in their composition of several toxic and carcinogenic chemical compounds, such as polycyclic aromatic hydrocarbons (PAHs) and metals, are linked to several respiratory diseases, including lung cancer. Epithelial-to-mesenchymal transition (EMT) is a crucial step in lung cancer progression, involving several morphological and phenotypical changes. The study aims to investigate how exposure to CDPs from different biomass sources might be involved in cancer development, focusing mainly on the effects linked to EMT and invasion on human A549 lung cells. Biomass combustion-derived particles (BCDPs) were collected from a stove fuelled with pellet, charcoal or wood, respectively. A time course and dose response evaluation on cell viability and pro-inflammatory response was performed to select the optimal conditions for EMT-related studies. A significant release of IL-8 was found after 72 h of exposure to 2.5 μg/cm2 BCDPs. The EMT activation was then examined by evaluating the expression of some typical markers, such as E-cadherin and N-cadherin, and the possible enhanced migration and invasiveness. Sub-acute exposure revealed that BCDPs differentially modulated cell viability, migration and invasion, as well as the expression of proteins linked to EMT. Results showed a reduction in the epithelial marker E-cadherin and a parallel increase in the mesenchymal markers N-cadherin, mainly after exposure to charcoal and wood. Migration and invasion were also increased. In conclusion, our results suggest that BCDPs with a higher content of organic compounds (e.g. PAHs) in their chemical composition might play a crucial role in inducing pro-carcinogenic effects on epithelial cells.

Lipotoxicity in human lung alveolar type 2 A549 cells: Mechanisms and protection by tannic acid.

Palmitic acid (PA) is a saturated free fatty acid which, when being excessive, accounts for lipotoxicity. Using human lung A549 cells as a model for lung alveolar type 2 epithelial cells, we found that challenge of A549 cells with PA resulted in apoptotic cell death, as reflected by positive annexin V and PI staining, and also appearance of cleaved caspase-3. PA treatment also caused depletion of intracellular Ca2+ store, endoplasmic reticulum (ER) stress, and oxidative stress. Tannic acid (TA), a polyphenol present in wines and many beverages, alleviated PA-induced ER stress, oxidative stress and apoptotic death. Thus, our results suggest PA lipotoxicity in lung alveolar type 2 epithelial cells could be protected by TA.

Cytotoxicity and Genotoxicity of Polystyrene Microplastics with Different Size and Surface Modification in A549 Human Lung Cells

Cytotoxicity and Genotoxicity of Polystyrene Microplastics with Different Size and Surface Modification in A549 Human Lung Cells

Effect of Lutein-Rich Extract on Human Cancer cells

Background: Lutein and its isomerzeaxanthin are safe natural compounds. They are able to reduce the development of tumor and other chronic diseases. The objectives of the current study was to examine the cytotoxicity of lutein isolated and purified from alfalfa, safe and low-cost plant, on five different human cancer cell lines, namely (MCF-7), (HepG2), (A549), (PC3), and (HCT116), as well as normal (HFB4) cells. Method: We examined the cytotoxicity of lutein purified from Medicago sativa L and evaluate its activity against human liver HepG2, breast MCF-7, lung A549, prostate PC3, and colon HCT116 cancer cell lines using SRB assay in comparison with doxorubicin as a reference drug. Results: Results revealed that the tested extract could be a more promising anticancer agent in the case of MCF-7 (IC50, 3.10±0.47 μg/ml) compared with standard drug doxorubicin (IC50, 2.90±0.30 μg/ml). Moreover, the extract showed a moderate effect on HepG2 (IC50, 6.11±0.84 μg/ml) versus doxorubicin (IC50, 2.90±0.30 μg/ml); meanwhile, the extract showed no activity against A549, PC3, and HCT116 cells. The results further revealed that the extract had no toxicity against the growth of normal HFB4 cells versus doxorubicin. Conclusion: Lutein-rich extract from alfalfa had a major antiproliferative role in breast MCF-7 and liver HepG2 compared to doxorubicin.

Addressable graphene encapsulation of wet specimens on a chip for optical, electron, infrared and X-ray based spectromicroscopy studies.

Label-free spectromicroscopy methods offer the capability to examine complex cellular phenomena. Electron and X-ray based spectromicroscopy methods, though powerful, have been hard to implement with hydrated objects due to the vacuum incompatibility of the samples and due to the parasitic signals from (or drastic attenuation by) the liquid matrix surrounding the biological object of interest. Similarly, for many techniques that operate at ambient pressure, such as Fourier transform infrared spectromicroscopy (FTIRM), the aqueous environment imposes severe limitations due to the strong absorption of liquid water in the infrared regime. Here we propose a microfabricated multi-compartmental and reusable hydrated sample platform suitable for use with several analytical techniques, which employs the conformal encapsulation of biological specimens by a few layers of atomically thin graphene. Such an electron, X-ray, and infrared transparent, molecularly impermeable and mechanically robust enclosure preserves the hydrated environment around the object for a sufficient time to allow in situ examination of hydrated bio-objects with techniques operating under both ambient and high vacuum conditions. An additional hydration source, provided by hydrogel pads lithographically patterned in the liquid state near/around the specimen and co-encapsulated, has been added to further extend the hydration lifetime. Note that the in-liquid lithographic electron beam-induced gelation procedure allows for addressable capture and immobilization of the biological cells from the solution. Scanning electron microscopy and optical fluorescence microscopy, as well as synchrotron radiation based FTIR and X-ray fluorescence microscopy, have been used to test the applicability of the platform and for its validation with yeast, A549 human carcinoma lung cells and micropatterned gels as biological object phantoms.

Development and characterization of Brigatinib loaded solid lipid nanoparticles: In-vitro cytotoxicity against human carcinoma A549 lung cell lines

Brigatinib (BG) is a tyrosine kinase receptor inhibitor act as an antineoplastic agent by blocking the action of an abnormal protein that causes cancer cells to multiply. In the current study, nine formulae of BG loaded solid lipid nanoparticles (SLNs) were developed using 32 factorial design. SLNs were prepared by the solvent emulsification technique using stearic acid as lipid and soya- lecithin as a surfactant, both of these act as independent variables, whereas Particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE) and drug loading (DL) were selected as responses. The particle size was found to be in the nano range (176−787 nm), fairly monodisperse (PDI indices 0.19−0.5), interparticle electrical stability was supported by zeta-potential (+1.78 mV to -15.4 mV), whereas EE and DL were in the range of (61.31–87.87 %) (3.35–31.01 %), respectively. Differential scanning calorimetry (DSC) thermograms indicated the amorphous state of BG in the SLN. Fourier transform infrared spectroscopy (FTIR) spectrums confirm non-interaction between drug and polymer while nuclear magnetic resonance (NMR) spectroscopy study revealed BG incorporation in the SLN. A scanning electron microscope (SEM) image exhibit a spherical shape of SLN. The in-vitro release profile demonstrates a sustained release pattern for the selected BS5 SLNs. MTT assay was performed on the optimized SLNs (BS5) and the results are indicative that BG loaded SLN (BS5) showed better cytotoxicity against A349 lung cell lines while compared to BG suspension and blank SLN. Thus, BG loaded SLNs can find Its better place in the non-small cell lung cancer treatment.

Investigating biological effects of multidimensional carboxylated carbon-based nanomaterials on human lung A549 cells revealed via non-targeted metabolomics approach

The biological responses of multidimensional carboxylated carbon-based nanomaterials (c-CBNs), including carboxylated graphene, carbon nanotube, and fullerene, on human lung A549 cells were investigated by using metabolomics technology. The structure and components of c-CBNs were characterized, and their biological effects were evaluated through cell apoptosis and viability analysis. Additionally, the metabolomics analysis of the nanomaterial-cell interaction system was performed using the established platform combining liquid chromatography-mass spectrometry (LC-MS) with the bioinformatics system. Results revealed that all tested c-CBNs demonstrated some biological effects in our cell model. However, significant metabolomic alterations induced by c-CBNs were also observed mainly in amino acids, organic acids, glycerophospholipids, and glycerolipids. Further, under the tested concentrations, the multiple dimensions of c-CBNs played a major role in determining the metabolic process in various interaction modes. This study provides an advanced alternative for evaluating metabolic effects of multidimensional nanomaterials through metabolomics technology considering the association between dimension and metabolic characteristics.

La3+/Sr2+ Dual-Substituted Hydroxyapatite Nanoparticles as Bone Substitutes: Synthesis, Characterization, In Vitro Bioactivity and Cytocompatibility.

The present study aims to synthesize biocompatible and bioactive lanthanum (La3+)/strontium (Sr2+) dual ion doped hydroxyapatite (HA) nanomaterials by sol-gel method. The discrete substitution of La3+ and Sr2+ in pure HA enhances the osteoconductivity. The co-substitution of various La3+ concentrations (0.03, 0.06 and 0.1 M) regulates the physical and In Vitro properties. The study also investigates the effect of La3+/Sr2+ substituents on the crystalline property, microstructure, photoluminescence and In Vitro bioactivity of HA samples. La3+/Sr2+ co-substitution decreases the crystallite size of HA without any significant distortion of the crystal structure. In addition, the dual ions doping influences nanoparticles morphology by reducing the particle size from 75 to 20 nm. The In Vitro bioactivity tests for the La3+/Sr2+ co-substituted HA confirm the osteoconductive boneapatite generating capacity. Bactericidal tests against Staphylococcus aureus and Pseudomonas aeruginosa stains show better resistivity of La3+/Sr2+-HA samples. To authenticate the biocompatibility and antimicrobial activity of the synthesized La3+/Sr2+ dual doped HA nanoparticles for bone implant applications, different tests like cell viability and toxicity were conducted using human lung A549 cells.