Durvalumab and taxane family combination therapy enhances the antitumoral effects for NSCLC: An in vitro study.

Immunotherapy has lately become the most preferred cancer treatment method, and for non-small cell lung cancer (NSCLC) first-line treatment, there are many immunotherapy options. This study aimed to assess the effectiveness and toxicity of paclitaxel (PTX), docetaxel (DTX) chemotherapy, immune checkpoint inhibitor treatment (durvalumab; DVL), and their combination in NSCLC. A-549 cells were treated with DVL in combination with PTX and DTX (a quarter of the IC50 ) to investigate their anticancer effects on these cells. The MTT assay, wound healing tests, and double-staining with Annexin V/PI were used to assess the cell viability, apoptosis, and migration. The results showed that a combination of 0.35 mg/mL DVL with 6.5 µg/mL PTX and 1.75 µg/mL DTX produced a synergistic effect with CI values of 0.88, 0.37, and 0.81, respectively. Moreover, the PTX + DTX + DVL combination led to a significantly increased apoptotic rate up to 88.70 ± 3.39% in the A549 cell line compared to monotherapy (p < .001). In addition, we found that the combination therapy with these agents increased the expression level of Bax, Cas-3, p53, and Bax/Bcl-2 ratio in all experimental groups. In conclusion, the results suggest that combining anti-PD-L1 antibody therapy with chemotherapy may provide a promising approach to enhance treatment outcomes and be a potentially efficacious strategy for treating NSCLC patients. Further research and clinical investigations are needed to elucidate the underlying molecular mechanisms and validate the therapeutic potential of these compounds in vivo.

Oxidative stress indices induced by industrial and urban PM2.5-bound metals in A549 cells.

The detrimental effects of atmospheric fine particulate matter (PM2.5) on human health are of major global concern. PM2.5-bound metals are toxic compounds that contribute to cellular damage. To investigate the toxic effects of water-soluble metals on human lung epithelial cells and their bioaccessibility to lung fluid, PM2.5 samples were collected from both urban and industrial areas in the metropolitan city of Tabriz, Iran. Oxidative stress indices, including proline content, total antioxidant capacity (TAC), cytotoxicity, and DNA damage levels of water-soluble components of PM2.5, were evaluated. Furthermore, an in vitro test was conducted to assess the bioaccessibility of various PM2.5-bound metals to the respiratory system using simulated lung fluid. PM2.5 average concentrations in urban and industrial areas were 83.11 and 97.71 µg/m3, respectively. The cytotoxicity effects of PM2.5 water-soluble constituents from urban areas were significantly higher than in industrial areas and the IC50 was found to be 96.76 ± 3.34 and 201.31 ± 5.96 µg/mL for urban and industrial PM2.5 samples, respectively. In addition, higher PM2.5 concentrations increased the proline content in a concentration-dependent manner in A549 cells, which plays a protective role against oxidative stress and prevents PM2.5-induced DNA damage. Also, the partial least squares regression revealed that Be, Cd, Co, Ni, and Cr, were significantly correlated with DNA damage and proline accumulation, which caused cell damage through oxidative stress. The results of this study showed that PM2.5-bound metals in highly polluted metropolitan city caused substantial changes in the cellular proline content, DNA damage levels and cytotoxicity in human lung A549 cells.

Simple fluorescence chemosensor for the detection of calcium ions in water samples and its application in bio-imaging of cancer cells.

This article describes the design, synthesis and characterization of a sensor suitable for practical measurement of ionized calcium in water samples and cancer cells. Calcium is an important ion in living organs and works as a messenger in several cellular functions. A lack of Ca ions interrupts the immune system and can lead to several diseases. A novel magnetic-polydopamine nanoparticle (PDNP)/rhodamine B (RhB)/folic acid (FA) nanoparticle was developed for the determination of calcium ions in MCF 7 cell lysates and water samples. Furthermore, the produced nanoparticle was employed for bioimaging of folate receptor (FR)-overexpressed cancer cells. This nanoprobe displayed a bright photoluminescence emission at 576 nm under an excitation wavelength of 420 nm. In the presence of calcium ions, the fluorescence emission of the MNPs-PDNPs/RhB/FA probe was proportionally decreased from 20 ng mL-1 to 100 ng mL-1 and 0.5 µg mL-1 to 20 µg mL-1 with a lower limit of quantification (LLOQ) of about 20 ng mL-1. The developed sensor showed a low-interference manner in the presence of possible coexistence interfering ions. In addition, this nanomaterial showed excellent biocompatibility with favorable differentiation ability to attach to the FR-positive cancer cells. The MNPs-PDNPs/RhB/FA nanoparticle has been utilized for bioimaging of the MCF 7 cell with favorable differentiation ability.

Improvement of anti-biofilm activities via co-delivery of curcumin and gentamicin in lipid-polymer hybrid nanoparticle.

Pseudomonas aeruginosa is the most common pathogen that causes chronic lung infections and recurrence of the disease in cystic fibrosis patients by hiding inside cells and biofilm matrix. Herein, we developed gentamicin and curcumin-loaded lipid-polymer hybrid nanoparticle- (termed CG-HNPs) to evaluate in vitro activities against biofilm-embedded P. aeruginosa and compared with lipid nanoparticles containing the same drugs (CG-Lip). The nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), fluorescence spectroscopy, and ultraviolet-visible (UV-vis) spectroscopy, which demonstrated that HNPs with a diameter of approximately 340 nm were uniform. The optimal CG-HNPs formulation illustrated high encapsulation (∼70%) and controlled release characteristics (gradually released in 72 h). The antibacterial activities of generated nanoparticles are maintained against planktonic and biofilm bacteria and it is effective in damage established biofilms. Besides, HNPs were biocompatible and nontoxic to J774 and HFF cell lines and uptake by the macrophages (J774), which facilitated the killing of intracellular bacteria in macrophages. These results introduced CG-HNPs as a promising antibacterial agent for the treatment of chronic infections and intracellular bacteria due to excellent antibacterial activity.

The influence of laser frequency and groove distance on cell adhesion, cell viability, and antibacterial characteristics of Ti-6Al-4V dental implants treated by modern fiber engraving laser.

OBJECTIVE: Micro-nano scale surface modification of Ti-6Al-4V was investigated through the fascinated modern fiber engraving laser method. The process was performed at a high laser speed of 2000mm/s, under different laser frequencies (20-160kHz) and groove distances (0.5-50µm). METHODS: Topographic evaluations such as Atomic Force Microscopy (AFM) and Field Emission Scanning Electron Microscopy (FE-SEM) were used to identify the quality and regularity of patterns. The proliferation of human osteoblast-like osteosarcoma cells (MG63) was analyzed by MTT assay for up to 72h. Also, the plate counting method was used to quantify the viability potential of the modified surface against Escherichia coli bacteria. RESULTS: The cellular viability of the sample modified at the laser frequency of 20kHz and grooving distance of 50µm increased up to 35 and 10% compared to the non-treated and control samples, respectively. In the case of the surface modification at lower grooving distances range between 0.5-50µm, the maximum laser frequency (160kHz) applied leads to lower pulse's energies and less bacterial adhesion. Otherwise, at groove distances more than 50µm, the minimum laser frequency (20kHz) applied reduces the laser pulse overlaps, increases the cell adhesion and antibacterial properties. SIGNIFICANCE: Surface modification by the fiber engraving laser process significantly enhances the cell adhesion on the surface. As a result of such roughness and cell adhesion enhancement, the surface toxicity feature diminished, and its antibacterial properties improved.

A novel iron quantum cluster confined in hemoglobin as fluorescent sensor for rapid detection of Escherichia coli.

A new method based on fluorescent probe of iron quantum cluster has been proposed for rapid detection of Escherichia coli (E. coli). The iron quantum cluster was synthesized using hemoglobin as both a source of iron and a protective agent (Hb-FeQCs). The investigation of the sensitivity of Hb-FeQCs towards metal ions showed a highly selective turn off fluorescence for Cu2+. It suggests that Cu2+ can induce fluorescence quenching by binding to amino acids of Hb. The ability of E. coli bacteria to capture and reduce of Cu ions caused to efficient recovery of the fluorescence of Hb-FeQCs from Cu2+-caused quenching. This probe has a satisfactorily linear range of 0.35-35 µM for Cu2+ under the optimal iron quantum cluster concentration (500 µg/mL) with an 85 nM detection limit. Rapid and facile detection of E.coli bacteria with the limit of detection around 8.3 × 103 CFU/mL was successfully achieved in the artificially contaminated urine, tap water, and DMEM samples within 30 min. The fluorescence recovery was investigated by different types of bacteria and only E. coli revealed 56% recovery which related to its capability to Cu2+ reduction and the great potential of the fluorescent probe for rapid detection of pathogenic E. coli bacteria. Furthermore, the Hb-FeQCs can detect E. coli bacteria in an infected urine sample by retrieving up to 74% of its fluorescence which is helpful to accelerate the diagnosis and treatment of urinary tract infection (UTI).

Chemiluminescent liposomes as a theranostic carrier for detection of tumor cells under oxidative stress.

Hydrogen peroxide (H2O2) is one of the main source of oxidative stress and a typical marker of reactive oxygen species (ROS)-associated diseases. Therefore, selective detection and scavenging of overproduced H2O2 provide enormous benefits to the successful treatment of ROS-related diseases. The authors took advantage of this property to detect cancer cells using chemiluminescent peroxyoxalate reaction. Here, a new contrast agent presented for hydrogen peroxide, termed peroxyoxalate liposomes, which detect hydrogen peroxide through chemiluminescence reaction, and have the physical/chemical properties needed for imaging applications. The peroxyoxalate liposomes are composed of Bis (2, 4, 6-trichlorphenyl) oxalate (TCPO) and curcumin as fluorophore. Experimental factors such as TCPO, imidazole, hydrogen peroxide and curcumin concentration were optimized. Moreover, application of curcumin makes it possible to design a system for selective tumor destruction. In the reaction of peroxyoxalate, it acts as an oxalate activator with intracellular hydrogen peroxide and experiences excitation as a result of the reaction. In addition, curcumin also acts as a photosensitizer (PS) causing cell damage. In the optimum conditions, the measurable concentration range of 0.86-220 µM of hydrogen peroxide were evaluated from the linear calibration curve with satisfactory RSD% and corresponding detection limits of 650 nM. Therefore, it has the sensitivity needed to detect physiological concentrations of hydrogen peroxide. Moreover, cellular uptake experiments showed that the liposomes enhance extravasation into permeable membranes and significantly increased the bioavailability of curcumin.