Cytotoxicity Experiments Research Articles

Comparison and Assessment of Anti-Inflammatory and Antioxidant Capacity Between EGCG and Phosphatidylcholine-Encapsulated EGCG.

To compare and evaluate the differences between EGCG and phosphatidylcholine-encapsulated EGCG in terms of their anti-inflammatory and antioxidant capacities. In this study, transdermal absorption experiments were conducted to compare the absorption capacity of EGCG and phosphatidylcholine-encapsulated EGCG. Subsequently, the disparity in anti-inflammatory and antioxidant efficacy between EGCG and phosphatidylcholine-encapsulated EGCG were evaluated through cytotoxicity experiments, as well as the determination of cellular inflammatory factors and the measurement of ROS content under different treatment conditions. The concentration of EGCG, encapsulated in phosphatidylcholine, in porcine skin is 40.76 ± 1.29 μg/cm2, which is significantly higher than the concentration of EGCG alone (31.62 ± 2.01 μg/cm2). Also, the ability of phosphatidylcholine-encapsulated EGCG to suppress inflammatory factors such as tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) was notably superior to that of EGCG alone. Both phosphatidylcholine-encapsulated EGCG and EGCG showed excellent ROS scavenging ability in terms of antioxidant capacity. The percutaneous absorption and anti-inflammatory impact of EGCG encapsulated within phosphatidylcholine were substantially enhanced when compared to EGCG by itself. Additionally, both formulations exhibited enhanced ROS scavenging capacities, albeit the variance between them was not pronounced. These insights furnish a vital theoretical underpinning for the utilization of phosphatidylcholine-encapsulated EGCG in cosmetic applications, specifically for fostering products with anti-inflammatory and antioxidant benefits.

Smart Cancer-Targeting and Super-Sensitive Sensing of Eu3+/Tb3+-Induced Hyaluronan Characteristic Nano-Micelles with Effective Drug Loading and Release

To avoid the critical problems of effective drugs not being carried to their targeted cancers and their quantity and location not being sensed in situ, this work presents a completely new innovative strategy to achieve both smart cancer targeting (SCT) and super-sensitive sensing (SSS), where one drug carrier works for effective drug loading and release. Herein, malignant melanoma treatment is used as an example of reliable detection and effective therapy. We report two characteristic dumbbell-like nano-micelles and spherical-like nano-micelles of hyaluronan induced by the Eu3+/Tb3+ complexes for effective drug loading and release, respectively. These special Eu3+/Tb3+-loaded nano-micelles (marked as ENM and TNM) have strong and sharp red/green luminescence that can sensitively detect the malignant melanoma drug dacarbazine through changes in fluorescence intensity. Cytotoxicity experiments confirmed that both ENM and TNM are not toxic to normal cells at very high concentrations of 4 mM. However, when loaded with cancer drugs (D-ENM and D-ENM), they both killed cancer cells with more than 40% efficacy at this concentration. The in vivo experiments confirmed that D-ENM and D-TNM can effectively target cancer cells in tissue and effectively impede cancer growth. The detection limits of ENM and TNM in sensing cancer drugs can reach 0.456 μg/mL and 0.139 μg/mL, respectively. Therefore, the reported Eu3+/Tb3+-induced hyaluronan nano-micelles (ENM and TNM) are distinguished carriers of this cancer drug and excellent in situ sensors, and they have highly therapeutic effects with extremely low toxicity to normal cells.

Stereolithography Printing and Mechanical Properties of Polyethylene Glycol Diacrylate/Hexagonal Boron Nitride Ceramic Composites

To enhance the mechanical properties of bioceramic composite bone scaffolds, a composite paste of polyethylene glycol diacrylate (PEGDA) and hexagonal boron nitride (h‐BN) with a solid content of up to 42 wt% was developed in this study. The part was produced using stereolithography (SLA). The SLA printing parameters and material ratios of the paste were optimized through a homogeneous design and mechanical property tests. The results indicate that the single‐line curing width of the PEGDA/h‐BN paste in the XY plane ranged from 172 to 209 μm, while the curing depth of a single layer along the Z‐axis ranged from 99 to 154 μm. Laser power was identified as the primary factor influencing both the width and depth of curing. The compressive strength of the printed sample of PEGDA/h‐BN ceramic composite paste was measured at 222.4 ± 5.6 MPa, which is 61 times greater than the compressive strength of a pure PEGDA structure and comparable to that of cortical bone (100‐230 MPa). Finally, the superior biocompatibility of PEGDA/h‐BN ceramics was confirmed through cytotoxicity experiments. Consequently, PEGDA/h‐BN ceramic composites meet the mechanical properties and biocompatibility requirements necessary for bone tissue applications, indicating promising potential in the field of bone tissue engineering.

Dodecanoyl-L-tryptophan: A Novel Natural Antibiotic Isolated from Mesophotic Sponge-associated Salinicola sp. LHM and its Biological Function

Background: Sponge-associated microbiota plays a crucial role in maintaining host health by providing chemical defense through the synthesis of diverse secondary metabolites. However, research on these secondary metabolites is still in its early stages. Objective: The present study aimed to investigate new natural antibiotics from mesophotic sponge symbiotic microbiota and explore its in vitro antibacterial activity and preliminary biological function. Methods: Bacteria strain Salinicola sp. LHM was isolated from sponge L. birotulata L26 and identified based on the 16S rRNA gene analysis. Subsequently, the strain was fermented using a liquid M9 medium and screened for antibiotics with an antibacterial guiding assay. Extensive chromatographic methods were introduced to isolate the target compound, and its chemical structure was elucidated by spectroscopic analysis (LC-MS, NMR). The minimum inhibitory concentration (MIC) and cytotoxicity experiments evaluated the isolated compound's biological activity. Furthermore, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and quartz crystal microbalance with dissipation (QCM-D) were used to study the bactericidal mechanism of DLT. Finally, the preliminary biological function was explored by performing the cell-feeding experiment. Results: We successfully identified one novel natural antibiotic, dodecanoyl-L-tryptophan (DLT), in Salinicola sp. LHM isolated from mesophotic sponge Lotrochota birotulata L26. DLT exhibited potent antibacterial activity against the Bacillus subtilis and Staphylococcus aureus, with MIC values of 32 μM and 16 μM, respectively. The bactericidal tests showed that DLT broke the cell membrane to cause cell death by leaking the cell's inner content. Furthermore, the cell-feeding experiment proved that DLT producer- Salinicola sp. LHM could feed on the inner content of death cells. In addition, DLT also exhibited cytotoxicity against bronchial epithelial cells BEAS-2B, with an EC50 value of 150 μM, indicating a favorable selectivity profile. result: We successfully identified one novel natural antibiotic, dodecanoyl-L-tryptophan (DLT), in Salinicola sp. LHM isolated from mesophotic sponge Lotrochota birotulata L26. DLT exhibited potent antibacterial activity against the Bacillus subtilis and Staphylococcus aureus, with MIC values of 32 μM and 16 μM, respectively. The bactericidal tests showed that DLT broke the cell membrane to cause cell death by leaking the cell's inner content. Furthermore, the cell-feeding experiment proved that DLT producer- Salinicola sp. LHM could feed on the inner content of death cells. In addition, DLT also exhibited cytotoxicity against bronchial epithelial cells BEAS-2B, with an EC50 value of 150 μM, indicating a favorable selectivity profile. Conclusion: This research identified one novel natural antibiotic DLT and provided initial insights into the chemical defense exerted by Salinicola sp. LHM with its secondary metabolite DLT.

Research on the Corrosion Resistance and Cytotoxicity of Medical Forged Co-28Cr-6Mo Alloy

Co-Cr-Mo alloy as a human body implant material has a long history, because of its excellent corrosion resistance and biocompatibility, and is widely used in human hip joint materials. Co-Cr-Mo alloy in the human body is often in a passivation state; the formation of dense oxide film on the alloy surface prevents further corrosion of the alloy. The main component of the passivation film is the oxide of Cr, so a layer of oxide film formed by Cr on the surface of Co-Cr-Mo alloy is the reason for its good corrosion resistance. In biocompatibility, cytotoxicity is the first choice and necessary option for biological evaluation, and cytotoxicity can quickly detect the effect of materials on cells in a relatively short time. Therefore, this research conducted a comparative evaluation on the corrosion resistance and biocompatibility of forged Co-Cr-Mo alloys produced in domestic and foreign alloys in line with medical standards. Three simulated human body fluids and Princeton electrochemical station were selected for corrosion resistance experiments, and it was found that the corrosion resistance of four alloys in sodium citrate solution inside and outside China would be reduced. All the alloys exhibit secondary passivation behavior in Hanks solution, which improves the corrosion resistance of the alloys. According to the self-corrosion potential Ecorr analysis, the corrosion resistance of domestic B alloy is the best, while that of foreign R31537 alloy is poor. In the biocompatibility experiment, the biocompatibility of Co-Cr-Mo alloy was evaluated through the measurement of contact Angle and cytotoxicity reaction. The experimental results show that Co-Cr-Mo alloy is a hydrophilic material, and the contact Angle of foreign R31537 alloy is smaller, indicating that the surface of R31537 alloy is more suitable for cell adhesion and spreading. According to the qualitative and quantitative analysis of the cytotoxicity experiment, the toxic reaction grade of domestic A, B and R31537 alloy is grade 1, the toxic reaction grade of C alloy is grade 2, and C alloy has a slight toxic reaction.

Metformin-mediated protection against doxorubicin-induced cardiotoxicity

BackgroundA phase II clinical trial of metformin (MET) for the treatment of doxorubicin (DOX)-induced cardiotoxicity (NCT02472353) failed. ObjectivesThe aims of this study were to confirm MET-mediated protection against DOX-induced cardiotoxicity and its mechanism using H9C2 cells, and to establish a Wistar rat model of DOX-induced cardiotoxicity. Subsequently, Wistar rats were utilized to identify clinically relevant indicators for evaluating MET-mediated protection against DOX-induced cardiotoxicity, thereby facilitating early transition towards successful clinical trials. MethodsMET-mediated protection was assessed using cell viability and cytotoxicity experiments. Additionally, intramitochondrial reactive oxygen species (ROS) levels were measured using an ROS fluorescent probe (dihydroethidium) to confirm the oxidative stress mechanism. Eighteen Wistar rats were randomly allocated to the control, DOX, and DOX+MET groups; and the body weight, adverse drug reactions (ADRs), myocardial injury, cardiac function, oxidative stress, and histopathology of heart tissues were compared between groups. ResultsH9C2 cells treated with MET/Dexrazoxane demonstrated dose-dependent protection against DOX-induced cardiotoxicity. The fluorescence intensity of H9C2 cells suggested DOX-induced cardiomyocyte toxicity and MET-mediated protection against DOX-induced cardiotoxicity. In vivo experiments confirmed that a rat model of DOX-induced cardiotoxicity was successfully established, but MET-mediated protection against DOX-induced cardiotoxicity was not demonstrated. This was attributed to insufficient energy intake because of ADRs, such as vomiting. ConclusionsWe confirmed the MET-mediated protection against DOX-induced cardiomyocyte toxicity and its mechanism involving the inhibition of oxidative stress in vitro experiments. It is imperative to investigate the optimal conditions for MET-mediated protection against DOX-induced cardiotoxicity in vivo or clinical trials.

Anticancer Efficacy of Biosynthesized Zinc Oxide and Gold Nanoparticles

Abstract Introduction/Objective Introduction: Advancements in nanoscale materials have led to the exploration of metal oxides for cancer diagnosis and therapy. Zinc oxide nanoparticles (ZnO NPs) and gold nanoparticles (Au NPs) are particularly promising due to their biocompatibility and anticancer properties demonstrated across various cancer cell lines. Objectives This study aimed to isolate fungal endophytes from Eucalyptus sideroxylon leaves and utilize them for the biosynthesis of nanoparticles (ZnO NPs and Au NPs) to assess their anticancer activity. Methods/Case Report Methods: Healthy Eucalyptus sideroxylon samples were collected from a desert research center, and endophytes were isolated and cultivated. The fungal biomass was processed to synthesize ZnO NPs and Au NPs. Cell lines were propagated for cytotoxicity experiments using the MTT assay in a 96-well plate format. Results (if a Case Study enter NA) Results: Biosynthesized ZnO and Au NPs exhibited anticancer activity against HCT-116 and CACO2 cell lines. The IC50 values for ZnO NPs were 5.06 μg/mL for HCT-116 and 6.07 μg/mL for CACO2, while Au NPs showed IC50 values of 5.9 μg/mL for HCT-116 and 1.1 μg/mL for CACO2. ZnO NPs demonstrated dose-dependent toxicity on HCT-116 cells, with increasing concentrations leading to a reduction in cell viability. Similarly, Au NPs exhibited dose-dependent cytotoxicity on both cell lines. Conclusion Conclusion: This study underscores the potential of endophytic fungi for biosynthesizing metal nanoparticles with significant anticancer effects. ZnO NPs displayed superior efficacy against colon cancer cells compared to Au NPs, indicating their potential as therapeutic agents. The findings highlight the importance of exploring natural sources for nanoparticle synthesis and their application in cancer therapy.

Preparation of Disulfide/Trisulfide Core-Cross-Linked Polycarbonate Nanocarriers for Intracellular Reduction-Triggered Drug Release.

Polymeric nanocarriers have attracted significant attention in the field of anticancer drug delivery due to their unique advantages. However, designing nanocarriers that can maintain stability in the bloodstream while achieving specific drug release within tumor cells remains a major challenge. To address this issue, constructing reversible cross-linked polymeric nanocarriers that are sensitive to the intracellular reducible glutathione (GSH) characteristic of the tumor microenvironment is a promising strategy. Based on this, we designed and synthesized two novel six-membered bicyclic carbonate monomers containing disulfide (DSBC) and trisulfide (TSBC) bonds. Through a one-step ring-opening polymerization, a series of reduction-sensitive polycarbonate copolymers (i.e., PEG-PDSBC and PEG-PTSBC) were prepared, and doxorubicin (DOX)-loaded nanoparticles were fabricated using a nanoprecipitation method. The in vitro drug release behaviors of these nanoparticles were systematically investigated. The results showed that these polymers, due to the cross-linked structure formed by the ring-opening polymerization of their bicyclic monomers, could self-assemble into stable nanoparticles. Under different concentrations of glutathione, DOX-loaded PEG-PTSBC nanoparticles demonstrated faster drug release, indicating more optimized intracellular drug release properties. Further cytotoxicity experiments revealed that both types of blank nanoparticles exhibited good biocompatibility with the 4T1 and NIH-3T3 cells. Fluorescence microscopy and flow cytometry results further indicated that DOX-loaded PEG-PTSBC nanoparticles released more drugs in 4T1 cells, significantly inhibiting tumor cell growth compared with DOX-loaded PEG-PDSBC nanoparticles, with no noticeable difference in NIH-3T3 normal cells. In conclusion, this study suggests that trisulfide cross-linked polycarbonate-based nanocarriers hold promise as an anticancer drug delivery system that combines stability in the bloodstream with specific intracellular drug release, offering new insights for the development of novel, efficient, and safe anticancer nanomedicines.

Construction of self-driving anti-αFR CAR-engineered NK cells based on IFN-γ and TNF-α synergistically induced high expression of CXCL10

IntroductionOvarian cancer is the most malignant gynecological tumor. Previous studies have demonstrated that chimeric antigen receptor (CAR)-engineered NK-92 cells targeting folate receptor α (αFR) (NK-92-αFR-CAR) can specifically kill αFR-positive ovarian cancer cells. However, the migration barrier restricts antitumor effects of CAR-engineered cells. ObjectivesTo elucidate the mechanism by which NK-92-αFR-CAR cells induce the secretion of chemokine CXCL10 during killing ovarian cancer cells. It is speculated that NK-92-αFR-CAR-CXCR3A can target αFR and have chemotaxis of CXCL10, and they may have stronger killing effect of ovarian cancer. MethodsStudy the mechanism of CXCL10 expression strongly induced by TNF-α and IFN-γ combined stimulation in ovarian cancer cells. Construct the fourth generation of NK-92-αFR-CAR-CXCR3A cells, which were co-expressed CXCR3A and αFR-CAR. Evaluate the killing and migration effects of NK-92-αFR-CAR-CXCR3A in vitro and in vivo. ResultsRNA sequencing (RNA-seq) first revealed that the expression level of the chemokine CXCL10 was most significantly increased in ovarian cancer cells co-cultured with NK-92-αFR-CAR. Secondly, cytokine stimulation experiments confirmed that IFN-γ and TNF-α secreted by NK-92-αFR-CAR synergistically induced high CXCL10 expression in ovarian cancer cells. Further signaling pathway experiments showed that IFN-γ and TNF-α enhanced the activation level of the IFN-γ-IFNGR-JAK1/2-STAT1-CXCL10 signaling axis. Cytotoxicity experiments showed that NK-92-αFR-CAR-CXCR3A cells could not only efficiently kill αFR-positive ovarian cancer cells in vitro but also secrete IFN-γ and TNF-α. Higher migration than that of NK-92-αFR-CAR was detected in NK-92-αFR-CAR-CXCR3A using transwell assay. NK-92-αFR-CAR-CXCR3A effectively killed tumor cells in different mouse xenograft models of ovarian cancer and increased infiltration into tumor tissue. ConclusionThis study confirmed that IFN-γ and TNF-α secreted by αFR-CAR-engineered NK cells can synergistically induce high expression of CXCL10 in ovarian cancer cells and constructed self-driving αFR-CAR-engineered NK cells that can break through migration barriers based on CXCL10, which may provide a new therapeutic weapon for ovarian cancer.

Water-based synthesis of dextran-methacrylate and its use to design hydrogels for biomedical applications

Polysaccharide-based hydrogels are desirable for biomedical applications owing to their biocompatibility and physicochemical tunability. The chemical modification of polysaccharides with photo-sensitive groups, such as methacrylates is a common method to obtain new hydrogel materials. This study introduces a non-toxic water-based method to effectively functionalize dextran with methacrylate groups. The methacrylation reaction with methacrylic anhydride in water in the presence of NaOH was rapid and efficient (85 % − 92 % yield), permitting degrees of substitution (DS) up to 62 % within 60 min. An unconventional solid-state photo-crosslinking method was employed to form chemically crosslinked dextran-based hydrogels with LAP (lithium phenyl-2,4,6-trimethylbenzoylphosphinate) as the photoinitiator. By varying the polymer formulations (DS, polymer mass, LAP concentration), a wide range of hydrogels were obtained with various swelling ratios (40–250 %) and release kinetics of model drug and protein biomolecules. Compression modulus values ranged from 32 ± 1 to 342 ± 10 MPa (dry state) and 87 to 8500 kPa (swollen state). Cytotoxicity experiments indicated good biocompatibility for the crosslinked dextran hydrogels. The green synthesis protocols and obtained dextran-based hydrogels with high mechanical strength open up perspectives for applications from tissue engineering to the design of medical devices such as microneedles.

Prediction, Design, Synthesis, Insecticidal Activities of Polysubstituted Pyridine Anthranilic Amide Derivatives

Based on the predicted structure, a series of polysubstituted pyridine compounds containing 5-(furan-2-yl)-1H-pyrazole-3-carboxamido were designed and synthesized. These compounds were characterized using 1H NMR, 13C NMR, 19F NMR and HRMS. The results of the bioassays indicated that certain compounds exhibited promising activities against Mythimna separata and Plutella xylostella. It is noteworthy that compound I-6 exhibited 47% insecticidal activity at a concentration of 0.01 μg/mL, which reached the same activity level as chlorantraniliprole (CHL).Moreover, the cytotoxicity experiment showed compound I-26 demonstrated 50% larvicidal activity against M. separata at 10 μg/mL. Moreover, the toxicity of I-26 (IC50 0.007365 μg/mL) was superior to that of CHL (IC50 1.059 μg/mL). Furthermore, molecular docking was employed to predict the binding positions of the compounds, which demonstrated a good correlation between their insecticidal activities and their binding values. Finally, DFT calculations and molecular docking were employed to refine the binding sites of the ryanodine receptors in M. separata with CHL and I-24. The research laid a foundation for the innovation of RyR insecticides in the future.

Unveiling the Mechanism of Compound Ku-Shen Injection in Liver Cancer Treatment through an Ingredient-Target Network Analysis.

Compound Ku-Shen Injection (CKI) is a traditional Chinese medicine preparation derived from Ku-Shen and Bai-Tu-Ling, commonly used in the adjunctive treatment of advanced cancers, including liver cancer. However, the underlying mechanisms of CKI's effectiveness in cancer treatment are not well defined. This study employs network pharmacology to investigate the traditional Chinese medicine (TCM) compatibility theory underlying CKI's action in treating liver cancer, with findings substantiated by molecular docking and in vitro experiments. Sixteen active components were identified from CKI, along with 193 potential targets for treating liver cancer. Key therapeutic target proteins, including EGFR and ESR1, were also identified. KEGG enrichment results showed that the neuroactive ligand-receptor interaction, cAMP signaling pathway, and serotonergic synapses make up the key pathway of CKI in the treatment of liver cancer. Molecular docking results confirmed that the key active ingredients effectively bind to the core targets. CCK-8 cytotoxic experiment results show that the CKI key components of oxymatrine and matrine can inhibit the growth of HepG2 liver cancer cell proliferation. A Western blot analysis revealed that oxymatrine suppresses the expression of EGFR, contributing to its therapeutic efficacy against liver cancer. our study elucidated the therapeutic mechanism of CKI in treating liver cancer and unveiled the underlying principles of its TCM compatibility through its mode of action.

A pH-modulated polymeric drug-release system simultaneously combats biofilms and planktonic bacteria to eliminate bacterial biofilm

Bacterial infection, leading to biofilm formation, raises grave concerns. With the aim of eliminating both integrity of biofilms and individual bacterial cells, it is desirable to develop bacterial biofilm-eliminating material to be combined with dispersal and anti-microbial agents. Herein, a biofilm-eliminating enzyme (α amylase) was incorporated in novel pH-sensitive polymer hydrogel, Poly (methacrylic acid-co-2-(dimethylamino)ethyl methacrylate), which encapsulates drug-loaded porous Zeolitic Imidazolate Framework-8 (ZIF-8). At body temperature (37 °C) the maximum swelling of the hydrogel was observed at pH 8.5, which assisted in rupturing biofilm by releasing α amylase. Amylase, encapsulated in polymer matrix reached 90% release after 6 days at 8.5, while CIP was released 96% on day 23 at pH 8.5. The antibiofilm activity of drug-releasing system was assessed against E. coli and S. aureus. The overall bacterial viability of biofilms showed significant time-dependent declines, when exposed to drug-loaded hydrogel. Importantly, cytotoxicity experiments showed excellent biocompatibility of hydrogel. In the in vivo deep wound infection model, drug-loaded hydrogel treatment showed complete wound closure with proper tissue regeneration. No inflammatory, or systemic toxicity of hydrogel was observed. The drug release from hydrogel is initiated only upon receiving physiological cue arising due to biofilm formation. Therefore, this hydrogel serves as reservoir for antibacterial drug, which release it only in presence of biofilm and thus work for sustained release for long period, compared to conventional drug loaded films or coatings. A powerful modality for management of biofilm-associated infections can be provided by the proposed synergistic strategy for complete elimination of biofilms.

Challenges in the Development of NK-92 Cells as an Effective Universal Off-the-Shelf Cellular Therapeutic.

The human-derived NK-92 cell-based CAR-NK therapy exhibits inconsistency with overall suboptimal efficacy and rapid invivo clearance of CAR-NK92 cells in cancer patients. Analysis indicates that although pre-existing IgM in healthy individuals (n = 10) strongly recognizes both NK-92 and CAR-NK92 cells, IgG and IgE do not. However, only a subset of cancer patients (3/8) exhibit strong IgM recognition of these cells, with some (2/8) showing pre-existing IgG recognition. These results suggest a natural immunoreactivity between NK-92 and CAR-NK92 cells and pre-existing human Abs. Furthermore, the therapy's immunogenicity is evidenced by enhanced IgG and IgM recognition postinfusion of CAR-NK92 cells. We also confirmed that healthy plasma's cytotoxicity toward these cells is reduced by complement inhibitors, suggesting that Abs may facilitate the rapid clearance of CAR-NK92 cells through complement-dependent cytotoxicity. Given that NK-92 cells lack known receptors for IgG and IgM, identifying and modifying the recognition targets for these Abs on NK-92 and CAR-NK92 cells may improve clinical outcomes. Moreover, we discovered that the 72nd amino acid of the NKG2D receptor on NK-92 cells is alanine. Previous studies have demonstrated polymorphism at the 72nd amino acid of the NKG2D on human NK cells, with NKG2D72Thr exhibiting a superior activation effect on NK cells compared with NKG2D72Ala. We confirmed this conclusion also applies to NK-92 cells by invitro cytotoxicity experiments. Therefore, reducing the immunoreactivity and immunogenicity of CAR-NK92 and directly switching NK-92 bearing NKG2D72Ala to NKG2D72Thr represent pressing challenges in realizing NK-92 cells as qualified universal off-the-shelf cellular therapeutics.

Harnessing Light for G-Quadruplex Modulation: Dual Isomeric Effects of an Ortho-Fluoroazobenzene Derivative.

G-quadruplexes (G4s) are important therapeutic and photopharmacological targets in cancer research. Small-molecule ligands targeting G4s offer a promising strategy to block DNA transactions and induce genetic instability in cancer cells. While numerous G4-ligands have been reported, relatively few examples exist of compounds whose G4-interactive binding properties can be modulated using light. Herein, we report the photophysical characterization of a novel ortho-fluoroazobenzene derivative, Py-Azo4F-3N, that undergoes reversible two-way isomerization upon visible light exposure. Using a combination of biophysical techniques, including affinity and selectivity assays, structural and computational analysis, and cytotoxicity experiments in cancer cell lines, we carefully characterized the G4-interactive binding properties of both isomers. We identify the trans isomer as the most promising form of interacting and stabilizing G4s, enhancing their ablation capability in cancer cells. Our research highlights the importance of light-responsive molecules in achieving precise control over G4 structures, demonstrating their potential in innovative anticancer strategies.

Green formulation of Menadione-loaded niosome as a skin-lightening preparation: In vitro/In vivo safety evaluation on Wistar rat

Purpose: In the present research, a green technique (an ultrasonic method) was used to synthesize menadione sodium bisulfite (MSB) niosome (Menasome) which is used to improve dermal delivery and increase anti-melanogenesis activities. Methods: Various cholesterol: surfactant (Chol: Sur) ratios were investigated to optimize the Menasomes. Photon correlation spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC) were employed to characterize the solid state of MSB in nanoparticle form. Additionally, the optimized formulation was used to investigate ex-vivo skin absorption, in vivo skin irritation, in vitro cell survival, and anti-melanogenesis activity. Results: The results exhibited that increasing cholesterol (Chol) declined the average size of the Menasomes from 653.766±25.171 nm to 298.133±8.823 nm and increased entrapment efficiency 30.237±3.4204% to 83.616±2.550 %. The rat skin permeation study indicated that Menasome gel administered more MSB in dermal layers (439.000±36.190μg/cm2 or 23.827±1.964%) than MSB plain gel (286.200± 22.6μg/cm2 or 15.53±1.227%). In both the in vivo skin irritation test and the in vitro cytotoxicity experiment, the extended-release behavior of the enhanced Menasome demonstrated a minimal side effect profile. Furthermore, optimum Menasome inhibited melanin formation (37.426± 1.644% at 15μM) greater than free MSB (57.383±1.654%) considerably (p <0.05). Furthermore, Menasome 7 prevented L-dopa auto-oxidation in higher levels (95.140±2.439%) than pure MSB solution (83.953±1.629%). Conclusion: According to the study's findings, the prepared Menasome could be employed as a viable nanovehicle for MSB dermal delivery, a promising solution for the management of human hyperpigmentation disorders.

Synthesis and photoluminescence properties of Ce3+/Tb3+ and Eu3+ ions doped GdB3O6/Ca10(PO4)6(OH)2 Core/Shell particles as well as its cytotoxicity against colon cancer cells

In this study, Ce3+/Tb3+ co-doped, Eu3+ doped GdB3O6 phosphor particles were synthesized by sol-gel method, coated with hydroxyapatite (HAP) and loaded with doxorubicin. Different chelating agents and surfactants (Cetyltrimethylammonium bromide (CTAB), citric acid, glycine, ethylenediaminetetraacetic acid (EDTA) and tartaric acid) were used in the synthesis in order to see their effect on the structure. While single phase Gadolinium triborate, GdB3O6 was obtained by using CTAB in precursor solution in the synthesis and Gadolinium orthoborate, GdBO3 produced when EDTA was used in precursor solution. Other organic molecules added to precursor solution produced mixtures of both phases. The highest photoluminescence intensity was obtained in the Gd0.95Ce0.025Tb0.025B3O6 and Gd0.825Eu0.175B3O6. In order to increase the drug loading efficiency, The Gd0.825Eu0.175B3O6 core was coated with Calcium hydroxyapatite, HAP. The core had an average size of 458.65 nm which increased to 616.85 nm after coating as seen with dynamic light scattering (DLS). Gd0.825Eu0.175B3O6@HAP particles were loaded with 7.82 % ± 0.80 wt doxorubicin and the release was studied at 37 °C in pH 7.4 phosphate-buffered saline (PBS) and pH 5.5 acetate buffer solutions. The total number of moles of drug released versus luminescence intensity was measured during the release studies and real-time imaging studies were carried out. Finally, cytotoxicity experiments were performed on HCT-116 colon cancer cells.

Role of gemini surfactants with biodegradable spacer as efficient capping agents of silver nanoparticles

Since the last decade, silver nanoparticles (AgNPs) continue to attract interest of both academia and industry due to their peculiar physical, chemical, and optical properties. In the field of pharmaceutical applications, they are efficient carriers in the processes of controlled drug release, improve the drug's bioavailability, act as efficient antimicrobial agents and provide other biological functions conveyed at the nanometric scale. The known issue hampering further development of applications of AgNPs is their instability in aqueous environment. The present study utilizes two series of cationic bisammonium gemini surfactants with two dodecyl chains and a biodegradable spacer containing two amide or ester groups for the stabilization of AgNPs. The presence of nanosilver in the dispersions was confirmed by UV–VIS plasmon resonance spectra. Stability of AgNPs was characterized by zeta potential measurements proving that amide and ester gemini surfactant series are able to effectively stabilize AgNPs. The particles size analysis utilizing dynamic light scattering and scanning electron microscopy showed that AgNPs stabilized with flexible ester-based gemini surfactants have their size smaller than those capped with amide-containing gemini surfactants. Antimicrobial and anti-inflammatory activity determination as well as cytotoxicity experiments with gemini surfactant stabilized AgNPs showed a complex dependence of biological activity of AgNPs on the molecular structure of stabilizing agents.

PH-Responsive supramolecular vesicles for imaging-guided drug delivery: Harnessing aggregation-induced emission.

The water-soluble tribenzotriquinacene-based hexacarboxylic acid ammonium salt, TBTQ-C 6 , acts as the host component (H) forming host-guest complexes with tetraphenylethylene (TPE)-functionalized monotopic and tetratopic quaternary ammonium derivatives, G1 and G2, to yield supra-amphiphiles. These supra-amphiphiles self-assemble to form pH-responsive fluorescent vesicles, which have allowed us to capitalize on the aggregation-induced emission (AIE) effect for imaging-guided drug delivery systems. These systems exhibit efficient drug loading and pH-responsive delivery capabilities. Upon encapsulation of the anticancer drug doxorubicin (DOX), both the TPE and DOX chromophores undergo dual-fluorescence deactivation due to the energy transfer relay (ETR) effect. Under acidic conditions, the release of DOX interrupts the ETR effect, resulting in the fluorescence recovery of TPE fluorogens and DOX, allowing for real-time visual monitoring of the drug release process. Cytotoxicity experiments confirmed the low toxicity of the unloaded vectors to normal cells, while the DOX-loaded vectors were found to significantly enhance the anticancer activity of DOX against cancer cells in vitro. The AIE-featured supramolecular vesicles presented in this research hold great potential for imaging-guided drug delivery systems.

Laser-zoned treatment of magnesium surfaces with predictable degradation applications

Magnesium metal is a promising material for medical applications due to its biocompatibility and similar modulus of elasticity to human bone. However, its complex corrosion process must be addressed before it can be used clinically to match post-implantation tissue repair. This study aims to regulate material degradation by utilizing laser surface treatment. The surface of pure magnesium was modified using nanosecond and femtosecond laser methods to create various micro-nanostructures, such as chain, streak, column, and groove structures. Surface roughness and wettability tests revealed that the groove structures had higher roughness values. All structures exhibited hydrophilicity, but the femtosecond laser-generated structures were more hydrophilic. Electrochemical tests and immersion experiments demonstrated that femtosecond laser modification significantly improved the corrosion resistance of magnesium metal compared to polished samples. Cytotoxicity experiments showed that the laser-treated magnesium was not cytotoxic. Based on the results, we constructed various structures on the magnesium rods in different regions. As a result, the rods exhibited multi-stage biodegradation behavior in simulated body fluids (SBF). This study presents a novel approach to controlling the degradation sequence of medical metals.