Combined oncolytic virotherapy gold nanoparticles as synergistic immunotherapy agent in breast cancer control.

Combining viruses and nanoparticles may be a way to successfully treat cancer and minimize adverse effects. The current work aimed to evaluate the efficacy of a specific combination of gold nanoparticles (GNPs) and Newcastle disease virus (NDV) to enhance the antitumor effect of breast cancer in both in vitro and in vivo models. Two human breast cancer cell lines (MCF-7 and AMJ-13) and a normal epithelial cell line (HBL-100) were used and treated with NDV and/or GNPs. The MTT assay was used to study the anticancer potentials of NDV and GNP. The colony formation assay and apoptosis markers were used to confirm the killing mechanisms of NDV and GNP against breast cancer cell lines. p53 and caspase-9 expression tested by the qRT-PCR technique. Our results showed that combination therapy had a significant killing effect against breast cancer cells. The findings demonstrated that NDV and GNPs induced apoptosis in cancer cells by activating caspase-9, the p53 protein, and other proteins related to apoptosis, which holds promise as a combination therapy for breast cancer.

Graphene oxide-induced, reactive oxygen species-mediated mitochondrial dysfunctions and apoptosis: high-dose toxicity in normal cells.

Aim: The cytotoxic effects of graphene oxide nanoparticles (GONPs) using MTT assays, observance of apoptotic markers, and oxidative stress were outlined. Materials & methods: Rat embryonic fibroblasts (REFs) and human epithelial breast cells (HBLs) were used at 250, 500 and 750 µg/ml concentrations. Results: Significant cytotoxic and apoptotic effects were observed. Analyses of CYP2E1 and malondialdehyde concentrations in REF and HBL-100 cell lines after exposing to GONPs confirmed the nanomaterials toxicity. However, the glutathione levels in REF and HBL-100 cell lines showed a substantial reduction compared with the control. The cytochrome CYP2E1, glutathione, malondialdehyde and caspase-3 alterations provided a plausible interlinked relationship. Conclusion: The study confirmed the GONPs cytotoxic effects on REF and HBL-100 cell lines. The outcome suggested caution in wide-spread applications of GONPs, which could have implications for occupational health also.

Catalytic, Theoretical, and Biological Investigations of Ternary Metal (II) Complexes Derived from L-Valine-Based Schiff Bases and Heterocyclic Bases.

A new series of ternary metal complexes, including Co(II), Ni(II), Cu(II), and Zn(II), were synthesized and characterized by elemental analysis and diverse spectroscopic methods. The complexes were synthesized from respective metal salts with Schiff's-base-containing amino acids, salicylaldehyde derivatives, and heterocyclic bases. The amino acids containing Schiff bases showed promising pharmacological properties upon complexation. Based on satisfactory elemental analyses and various spectroscopic techniques, these complexes revealed a distorted, square pyramidal geometry around metal ions. The molecular structures of the complexes were optimized by DFT calculations. Quantum calculations were performed with the density functional method for which the LACVP++ basis set was used to find the optimized molecular structure of the complexes. The metal complexes were subjected to an electrochemical investigation to determine the redox behavior and oxidation state of the metal ions. Furthermore, all complexes were utilized for catalytic assets of a multi-component Mannich reaction for the preparation of -amino carbonyl derivatives. The synthesized complexes were tested to determine their antibacterial activity against E. coli, K. pneumoniae, and S. aureus bacteria. To evaluate the cytotoxic effects of the Cu(II) complexes, lung cancer (A549), cervical cancer (HeLa), and breast cancer (MCF-7) cells compared to normal cells, cell lines such as human dermal fibroblasts (HDF) were used. Further, the docking study parameters were supported, for which it was observed that the metal complexes could be effective in anticancer applications.

In Vitro and In Vivo Functional Viability, and Biocompatibility Evaluation of Bovine Serum Albumin-Ingrained Microemulsion: A Model Based on Sesame Oil as the Payload for Developing an Efficient Drug Delivery Platform.

Combination of bovine serum albumin with microemulsions as constituting ingredient biopolymer has long been regarded an innovative method to address the surface functionalization and stability issues in the targeted payload deliveries, thereupon producing effectively modified microemulsions, which are superior in loading capacity, transitional and shelf-stability, as well as site-directed/site-preferred delivery, has become a favored option. The current study aimed to develop an efficient, suitable and functional microemulsion system encapsulating sesame oil (SO) as a model payload towards developing an efficient delivery platform. UV-VIS, FT-IR, and FE-SEM were used to characterize, and analyze the developed carrier. Physicochemical properties assessments of the microemulsion by dynamic light scattering size distributions, zeta-potential, and electron micrographic analyses were performed. The mechanical properties for rheological behavior were also studied. The HFF-2 cell line and hemolysis assays were conducted to ascertain the cell viability, and in vitro biocompatibility. The in vivo toxicity was determined based on a predicted median lethal dose (LD50) model, wherein the liver enzymes' functions were also tested to assess and confirm the predicted toxicity.

Catalytic response and molecular simulation studies in the development of synthetic routes in trimeric triaryl pyridinium type ionic liquids.

Under conventional and silica-supported Muffle furnace methods, water-soluble substituted trimeric triaryl pyridinium cations with various inorganic counter anions are synthesized. The solvent-free synthesis method is superior to the conventional method in terms of non-toxicity, quicker reaction times, ease of workup, and higher yields. Trimeric substituted pyridinium salts acted as excellent catalytic responses for the preparation of Gem-bisamide derivatives compared with available literature. To evaluate the molecular docking, benzyl/4-nitrobenzyl substituted triaryl pyridinium salt compounds with VEGFR-2 kinase were used with H-bonds, π-π stacking, salt bridges, and hydrophobic contacts. The results showed that the VEGFR-2 kinase protein had the most potent inhibitory activity. Intriguingly, the compound [NBTAPy]PF6- had a strongly binds to VEGFR-2 kinase and controlled its activity in cancer treatment and prevention.

Investigating the Effects of Biogenic Zinc Oxide Nanoparticles Produced Using Papaver somniferum Extract on Oxidative Stress, Cytotoxicity, and the Induction of Apoptosis in the THP-1 Cell Line.

This study investigated the effect of novel zinc oxide nanoparticles (ZnO NPs) biosynthesized employing Papaver somniferum leaf on oxidative stress, necrosis, and apoptosis in the leukemia cancer THP-1 cell. The obtained ZnO was examined using SEM, AFM, and TEM microscopy, which revealed an irregular spherical morphology with a size ranging from 20 to 30 nm, and the UV-vis absorbance revealed a strong absorption peak in the range of 360-370, nm confirming the production of ZnO NPs. THP-1 cells were subjected to an MTT, an EdU proliferation, a lactate dehydrogenase release tests, a reactive oxygen species (ROS) induction experiment, a DAPI staining detection assay, and a flow cytometric analysis for Annexin V to measure the effects of ZnO NPs on cancer cell growth inhibition, apoptosis, and necrosis. Our results show that ZnO NPs inhibit THP-1 line in a concentration-dependent pattern. It was observed that ZnO NPs triggered necrosis (cell death) and apoptosis in the cell line. ZnO NPs massively improved the formation of intracellular ROS, which is crucial in deactivating the development of leukemic cells. In conclusion, ZnO nanoparticles synthesized using Papaver somniferum extract have the ability to inhibit proliferation leukemic cancer cells, making them potential anticancer agents.

Folate-methotrexate loaded bovine serum albumin nanoparticles preparation: an in vitro drug targeting cytokines overwhelming expressed immune cells from rheumatoid arthritis patients.

The study planned to estimate biological parameters linked to rheumatoid arthritis (RA) patients, detecting the influence of MTX and biotherapy treatments on these parameters and synthesizing methotrexate bovine serum albumin nanoparticles linked to folate (FA-MTX-BSA NPs) to reduce the overwhelming expression of inflammatory cytokines. Inflammatory parameters showed significant increases in newly diagnosed and MTX-receiving groups while no changes were observed in the biotherapy-maintained group. MTX-loaded BSA nanoparticles were fabricated by the desolvation method and further linked to activated folic acid to obtain FA-MTX-BSA NPs. FA-MTX-BSA NPs were successfully characterized within the nanoscale range using different screening techniques. FA-MTX-BSA NPs showed an in vitro release in a sustained manner. The potential of MTX, MTX-BSA NPs, and FA-MTX-BSA NPs in inducing cytokine level reduction was detected. Significant decreases in interleukin- 1 beta (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels were obtained in cultures treated with FA-MTX-BSA NPs compared to the untreated culture in a dose-dependent pattern. Furthermore, FA-MTX-BSA NPs comparing with MTX and MTX-BSA NPs exhibited a significant advanced effect in decreasing cytokines levels. Accordingly, the conjunction of BSA NPs and MTX linked to folate potentially reduced cytokines manifestation in RA.

Recent Advances in Plant-Mediated Zinc Oxide Nanoparticles with Their Significant Biomedical Properties.

Compared to traditional physical and chemical approaches, nanobiotechnology and plant-based green synthesis procedures offer significant advantages, as well as having a greater range of medical and biotechnological applications. Nanoparticles of zinc oxide (ZnO NPs) have recently been recognized as a promising option for many industries, including optics, electrics, packaged foods, and medicine, due to their biocompatibility, low cytotoxicity, and cost-effectiveness. Several studies have shown that zinc ions are important in triggering cell apoptosis by promoting the generation of reactive oxygen species (ROSs) and releasing zinc ions (Zn2+), which are toxic to cells. The toxic nature of the chemicals used in the synthesis of ZnO nanoparticles limits their clinical utility. An overview of recent developments in green ZnO NP synthesis is presented in this review, emphasizing plant parts as reducing agents and their medical applications, including their antimicrobial, anticancer, antioxidant, and anti-inflammatory properties, as well as key mechanisms of action for these applications to facilitate further research on the biomedical fields in the future.

Biosynthesis of copper oxide nanoparticles mediated Annona muricata as cytotoxic and apoptosis inducer factor in breast cancer cell lines.

This study investigated for the first time a simple bio-synthesis approach for the synthesis of copper oxide nanoparticles (CuO NPs) using Annona muricata L (A. muricata) plant extract to test their anti-cancer effects. The presence of CuONPs was confirmed by UV-visible spectroscopy, Scanning electron microscope (SEM), and Transmission electron microscope (TEM). The antiproliferative properties of the synthesized nanoparticles were evaluated against (AMJ-13), (MCF-7) breast cancer cell lines, and the human breast epithelial cell line (HBL-100) as healthy cells. This study indicates that CuONPs reduced cell proliferation for AMJ-13 and MCF-7. HBL-100 cells were not significantly inhibited for several concentration levels or test periods. The outcomes suggest that the prepared copper oxide nanoparticles acted against the growth of specific cell lines observed in breast cancer. It was observed that cancer cells had minor colony creation after 24 h sustained CuONPs exposure using (IC50) concentration for AMJ-13 was (17.04 µg mL-1). While for MCF-7 cells was (18.92 µg mL-1). It indicates the uptake of CuONPs by cancer cells, triggering apoptosis. Moreover, treatment with CuONPs enhanced Lactate dehydrogenase (LDH) production, probably caused by cell membrane damage, creating leaks comprising cellular substances like lactate dehydrogenase. Hence, research results suggested that the synthesized CuONPs precipitated anti-proliferative effects by triggering cell death through apoptosis.

Gene expression and apoptosis response in hepatocellular carcinoma cells induced by biocompatible polymer/magnetic nanoparticles containing 5-fluorouracil

BACKGROUND: Super-paramagnetic iron oxide nanoparticles (SPION) contain a chemotherapeutic drug and are regarded as a promising technique for improving targeted delivery into cancer cells. RESULTS: In this study, the fabrication of 5-fluorouracil (5-FU) was investigated with loaded Dextran (DEXSPION) using the co-precipitation technique and conjugated by folate (FA). These nanoparticles (NPs) were employed as carriers and anticancer compounds against liver cancer cells in vitro. Structural, magnetic, morphological characterization, size, and drug loading activities of the obtained FA-DEX-5-FUSPION NPs were checked using FTIR, VSM, FESEM, TEM, DLS, and zeta potential techniques. The cellular toxicity effect of FA-DEX-5-FU-SPION NPs was evaluated using the MTT test on liver cancer (SNU-423) and healthy cells (LO2). Furthermore, the apoptosis measurement and the expression levels of NF-1, Her-2/neu, c-Raf-1, and Wnt-1 genes were evaluated post-treatment using flow cytometry and RT-PCR, respectively. The obtained NPs were spherical with a suitable dispersity without noticeable aggregation. The size of the NPs, polydispersity, and zeta were 74 ± 13 nm, 0.080 and 45 mV, respectively. The results of the encapsulation efficiency of the nano-compound showed highly colloidal stability and proper drug maintenance. The results indicated that FA-DEX-5-FU-SPION demonstrated a sustained release profile of 5-FU in both phosphate and citrate buffer solutions separately, with higher cytotoxicity against SNU-423 cells than against other cells types. These findings suggest that FA-DEX-SPION NPs exert synergistic effects for targeting intracellular delivery of 5-FU, apoptosis induction, and gene expression stimulation. CONCLUSIONS: The findings proved that FA-DEX-5-FU-SPION presented remarkable antitumor properties; no adverse subsequences were revealed against normal cells.

Pt(II)-Thiocarbohydrazone Complex as Cytotoxic Agent and Apoptosis Inducer in Caov-3 and HT-29 Cells through the P53 and Caspase-8 Pathways.

In this study, a platinum(II) complex ([Pt(H2L)(PPh3)] complex) containing a thiocarbohydrazone as the ligand was tested as an anti-proliferative agent against ovarian adenocarcinoma (Caov-3) and human colorectal adenocarcinoma (HT-29) through MTT assays. Apoptotic markers were tested by the AO/PI double staining assay and DNA fragmentation test. Flow cytometry was conducted to measure cell cycle distribution, while the p53 and caspase-8 pathways were tested via immunofluorescence assay. Results demonstrated that the cytotoxic effect of the Pt(II)-thiocarbohydrazone complexes against Caov-3 and HT-29 cells was highly significant, and this effect triggered the activation of the p53 and caspase-8 pathways. Besides, apoptosis stimulated by the Pt(II)-thiocarbohydrazone complex was associated with cell cycle arrest at the G0/G1 phase. These findings suggest that the target complex inhibited the proliferation of Caov-3 and HT-29 cells, resulting in the arrest of the cell cycle and induction of apoptosis via the stimulation of the p53 and caspase-8 pathways. The present data suggests that the Pt(II)-thiocarbohydrazone complex could also be a promising chemotherapeutic agent for other types of cancer cells.

Smart Nanoformulation Based on Polymeric Magnetic Nanoparticles and Vincristine Drug: A Novel Therapy for Apoptotic Gene Expression in Tumors.

BACKGROUND: Advanced nanobiotechnology provides safe and efficient drug delivery systems to deliver chemotherapy that targets cancer cells efficiently. METHODS: A polymeric-magnetic nanocarrier was composed of a dextran (DEX) shell, a superparamagnetic iron oxide (SPION) core and was conjugated with folate (FA) to carry the anticancer drug vincristine (VNC) in Tera-1 testicular tumor cells. The molecular mechanisms by which apoptosis was induced were analyzed using flow cytometry and qPCR, which exhibited anticancer activity of nanoparticles (NPs). RESULTS: This nanocarrier revealed a controlled release of VNC in citrate and phosphate buffer solutions that were maintained at pH 5.5 and pH 7.4, respectively. The Inhibitory concentration (IC50) values were greater than 5 mg/mL and displayed ten times higher cytotoxicity than the comparable free drug concentration. The Caspase-9 and P53 expressions were increased, whereas P21 and AKt1 decreased noticeably in the treated cells. The results point to the possible activation of apoptosis following treatment with NPs loaded with vincristine.

Design and Synthesis of Multi-Functional Superparamagnetic Core-Gold Shell Coated with Chitosan and Folate Nanoparticles for Targeted Antitumor Therapy.

A dual-targeting nanomedicine composed of pH-sensitive superparamagnetic iron oxide core-gold shell SPION@Au, chitosan (CS), and folate (FA) was developed as a doxorubicin (DOX) antitumor medication. Microemulsion was used for preparation and cross-linking conjugation. The characteristics of the designed nanocomposite were studied using atomic force microscopy (AFM), transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction, UV-visible spectroscopy, Zeta potential and vibrating sample magnetometry (VSM), and Fourier transform infrared spectroscopy. The prepared SPION@Au-CS-DOX-FA nanoparticles (NPs) were spherical with an average diameter of 102.6 ± 7 nm and displayed an elevated drug loading behavior and sustained drug release capacity. The SPION@Au-CS-DOX-FA NPs revealed long term anti-cancer efficacy due to their cytotoxic effect and apoptotic inducing efficiency in SkBr3 cell lines. Additionally, Real-time PCR outcomes significantly showed an increase in BAK and BAX expression and a decrease in BCL-XL and BCL-2. In vivo results revealed that SPION@Au significantly decreased the tumor size in treated mice through magnetization. In conclusion, prepared SPION@Au-CS-DOX-FA could be a beneficial drug formulation for clinical breast cancer treatment.

Linalool-Loaded Glutathione-Modified Gold Nanoparticles Conjugated with CALNN Peptide as Apoptosis Inducer and NF-κB Translocation Inhibitor in SKOV-3 Cell Line.

BACKGROUND: Linalool is a monoterpene compound with various potential therapeutic applications in several medical fields. Previous studies have indicated the activity of linalool against cell lines; however, its high level of toxicity restricts its use. The aim of this study was to design and manufacture compounds with a novel structure that can be used for loading linalool, to reduce its toxicity and improve its reachable ability. METHODS: We synthesized and characterized a new molecule for loading linalool onto gold nanoparticles (GNPs) capped with glutathione and conjugated with a CALNN peptide. Linalool was loaded onto the GNPs via the reaction of the surface groups of both linalool and the GNPs. Moreover, the target peptide could be loaded onto the surface of the GNPs via a chemical reaction. The cytotoxic effects of linalool-GNP (LG) and linalool-GNP-CALNN peptide (LGC) conjugates against ovarian cancer cells were investigated, as were the possible mechanisms underlying the induction of apoptosis. RESULTS: Our findings illustrated the significant antiproliferative effect of LG and LGC on SKOV-3 cells. The cytotoxicity assay demonstrated that LG and LGC were selectively toxic in cancer cells and induced apoptosis by activating caspase-8, the p53 protein, and various proteins involved in apoptosis. The present data demonstrated that LG and LGC have a high therapeutic potential and should be given particular consideration as anticancer drug-delivery systems, as LG and LGC were remarkably more cytotoxic against a cancer cell line than were linalool and GNPs alone. CONCLUSION: We concluded that LG and LGC are promising compounds that can be used for treating ovarian cancer (SKOV-3) cells via the induction of apoptosis through extrinsic and intrinsic pathways.

Antibacterial Activity of Honey/Chitosan Nanofibers Loaded with Capsaicin and Gold Nanoparticles for Wound Dressing.

This paper describes the preparation, characterization, and evaluation of honey/tripolyphosphate (TPP)/chitosan (HTCs) nanofibers loaded with capsaicin derived from the natural extract of hot pepper (Capsicum annuumL.) and loaded with gold nanoparticles (AuNPs) as biocompatible antimicrobial nanofibrous wound bandages in topical skin treatments. The capsaicin and AuNPs were packed within HTCs in HTCs-capsaicin, HTCs-AuNP, and HTCs-AuNPs/capsaicin nanofibrous mats. In vitro antibacterial testing against Pasteurella multocida, Klebsiella rhinoscleromatis,Staphylococcus pyogenes, and Vibrio vulnificus was conducted in comparison with difloxacin and chloramphenicol antibiotics. Cell viability and proliferation of the developed nanofibers were evaluated using an MTT assay. Finally, in vivo study of the wound-closure process was performed on New Zealand white rabbits. The results indicate that HTCs-capsaicin and HTCs-AuNPs are suitable in inhibiting bacterial growth compared with HTCs and HTCs-capsaicin/AuNP nanofibers and antibiotics (P < 0.01). The MTT assay demonstrates that the nanofibrous mats increased cell proliferation compared with the untreated control (P < 0.01). In vivo results show that the developed mats enhanced the wound-closure rate more effectively than the control samples. The novel nanofibrous wound dressings provide a relatively rapid and efficacious wound-healing ability, making the obtained nanofibers promising candidates for the development of improved bandage materials.

Investigation of Dextran-Coated Superparamagnetic Nanoparticles for Targeted Vinblastine Controlled Release, Delivery, Apoptosis Induction, and Gene Expression in Pancreatic Cancer Cells.

In the current study, the surface of superparamagnetic iron oxide (SPION) was coated with dextran (DEX), and conjugated with folic acid (FA), to enhance the targeted delivery and uptake of vinblastine (VBL) in PANC-1 pancreatic cancer cells. Numerous analyses were performed to validate the prepared FA-DEX-VBL-SPION, such as field emission scanning transmission electron microscopy, high-resolution transmission electron microscopy, dynamic light scattering (DLS), Zeta Potential, Fourier transform infrared spectroscopy, and vibrating sample magnetometry (VSM). The delivery system capacity was evaluated by loading and release experiments. Moreover, in vitro biological studies, including a cytotoxicity study, cellular uptake assessment, apoptosis analysis, and real-time PCR, were carried out. The results revealed that the obtained nanocarrier was spherical with a suitable dispersion and without visible aggregation. Its average size, polydispersity, and zeta were 74 ± 13 nm, 0.080, and -45 mV, respectively. This dual functional nanocarrier also exhibited low cytotoxicity and a high apoptosis induction potential for successful VBL co-delivery. Real-time quantitative PCR analysis demonstrated the activation of caspase-3, NF-1, PDL-1, and H-ras inhibition, in PANC-1 cells treated with the FA-VBL-DEX-SPION nanostructure. Close inspection of the obtained data proved that the FA-VBL-DEX-SPION nanostructure possesses a noteworthy chemo-preventive effect on pancreatic cancer cells through the inhibition of cell proliferation and induction of apoptosis.