Enhancement of the effect of novel targeted 5-aminolevulinic acid conjugated bismuth oxide nanoparticles-based photodynamic therapy by simultaneous radiotherapy on KB cells.

BACKGROUND: Selective accumulation of photosensitizers into cancerous cells is one of the most important factors affecting photodynamic therapy (PDT) efficacy. 5-aminolevulinic acid (5-ALA) is the precursor of a strong photosensitizer, protoporphyrin-IX; but it has poor permeability into the cells. Folate receptors are overexpressed on the surface of many tumor cells. In the present study, folic acid (FA) and 5-ALA conjugated bismuth oxide nanoparticles were synthesized; and used in PDT, radiotherapy (RT), and concurrent PDT & RT against nasopharyngeal carcinoma (KB cell line). METHODS: The KB cells were incubated with the synthesized nanoparticles (NPs) for 2 h; then illuminated using a custom-made LED lamp at the light dose of 26 J/cm2. Irradiation of the cells was carried out using X-ray 6 MV (2 Gy); and synergistic effect of the simultaneous RT and PDT treatments was evaluated using fractional product values. Efficacy of the treatments was determined using MTT and Caspase-3 enzyme activity assays. RESULTS: Targeting of folic acid receptors enables the selective endocytosis of the conjugated NPs. RT results in the presence of Bi2O3 NPs showed a significant radiosensitizer potential of these NPs. Fractional product values of 1.49±0.05, 1.36±0.06, and 1.05±0.06 obtained in the presence of FA-5-ALA conjugated NPs, 5-ALA conjugated NPs, and in the absence of the NPs, respectively. Therefore, simultaneous RT and PDT in the presence of these conjugated NPs is superior to RT in the presence of the NPs. CONCLUSION: Simultaneous PDT and RT in the presence of FA-5-ALA conjugated bismuth oxide NPs can be introduced as a promising therapeutic approach in controlling KB cancer cells.

Formulation and antibacterial properties of lollipops containing of chitosan- zinc oxide nano particles on planktonic and biofilm forms of Streptococcus mutans and Lactobacillus acidophilus.

This study aimed to formulate and characterize the experimental lollipops containing chitosan- zinc oxide nanoparticles (CH-ZnO NPs) and investigate their antimicrobial effects against some cariogenic bacteria. The CH-ZnO NPs were synthesized and characterized by X-ray diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR) analysis, and Transmission electron microscope (TEM). Then, four groups were made, including lollipops coated with 2 and 4 ml of CH-ZnO NPs, 0.7 ml CH-ZnO NPs incorporated lollipops, and those with no CH-ZnO NPs. Their antibacterial effectiveness against Streptococcus mutans and Lactobacillus acidophilus was evaluated by direct contact test and tissue culture plate method in planktonic and biofilm phases, respectively. Chlorhexidine mouthrinse (CHX) was used as a positive control group. In the planktonic phase, the antibacterial properties of both groups coated with CH-ZnO NPs were comparable and significantly higher than incorporated ones. There was no significant difference between CHX and the lollipops coated with 4 ml of NPs against S. mutans and CHX and two coated groups against L. acidophilus. None of the experimental lollipops in the biofilm phase could reduce both bacteria counts. The experimental lollipops coated with 2 and 4 ml of CH-ZnO NPs could reveal favorable antimicrobial properties against two cariogenic bacteria in the planktonic phase.

Improving the corrosion behavior of magnesium alloys with a focus on AZ91 Mg alloy intended for biomedical application by microstructure modification and coating.

Magnesium alloys such as AZ91 have received much attention due to their attractive properties, including biocompatibility and lightness. Although magnesium is a potential candidate for implant application, due to its rapid degradation in the physiological environment, there are still some challenges to using it as biocompatible implants. In this regard, various techniques such as microstructure modification and coating are utilized to moderate the degradation rate of magnesium alloys. Therefore, efforts are being made to conduct more extensive research to produce magnesium implants with acceptable corrosion resistance. In this literature review, an overview of the history of research on the corrosion behavior, biodegradability, microstructure deformation mechanisms, crystallographic texture in magnesium alloys with a focus on AZ91 Mg alloy, is provided. In addition, the necessity of improving the properties of AZ91 Mg alloy by the two methods of improving microstructure and coating, and existing innovations in these methods are investigated.

Methods of green synthesis of Au NCs with emphasis on their morphology: A mini-review.

Greener synthetic methods are becoming more popular as a means of reducing environmental pollution caused by reaction byproducts. Another important advantage of green methods is their low cost and the abundance of raw materials. Herein, we investigate the green Au nanoclusters (NCs) using microorganisms (bacteria and fungi) and plant extraction with various shapes and development routes. Natural products derived from plants, tea, coffee, banana, simple amino acids, enzyme, sugar, and glucose have been used as reductants and as capping agents during synthesis in literature. The synthesis techniques are generally chemical, physical and green methods. Green synthesis of Au NCs using bacteria and fungi can be divided into intracellular and extracellular. In an intracellular manner, bacterial cells are implanted in a culture medium containing salt and heated under suitable growth conditions. However, in an extracellular manner, the Au ions are directed from the outside into the cell. Thus, these methods are considered as a better alternative to chemical and physical synthesis. The research on green synthesis of Au nanoparticles (NPs) and its influence on their size and morphology are summarized in this review.

Ratiometric bioassay and visualization of dopamine ß-hydroxylase in brain cells utilizing a nanohybrid fluorescence probe.

Dopamine ß-hydroxylase (DBH) is involved in various neuronal transmission processes in the brain. Due to the severe diseases caused by abnormity levels of such important enzyme in human serum, sensitive and rapid detection of DBH at early stages is crucial, particularly for clinical analysis. Herein, we developed optical sensors for DBH that include the following: (i) a ratiometric fluorescence sensor that hybridizes the bovine serum albumin (BSA)-gold nanoclusters (BSA-AuNCs) and nitrogen doped carbon dots (N-CDs). The sensor proved to be highly selective and sensitive, achieving a linear range of 0.02-0.16 µg mL-1 and a limit of detection of 4.0 ng mL-1. In the presence of DBH, the fluorescence intensity of BSA-AuNCs (λem = 615 nm) was remarkably quenched by DBH serving as a reporter signal, whereas the N-CDs fluorescence intensity at 440 nm was almost kept unchanged serving as a reference signal. The developed ratiometric sensor is capable of demonstrating a color change from pink to violet and blue with a gradual increase in DBH concentration, which is discernible by the naked-eye. A test strip is prepared for semi-quantitative assay and convenient use. Intriguingly, by taking advantage of the inter-AuNCs aggregation in the presence of DBH, (ii) a resonance light scattering (RLS) sensor was also developed based on the nanohybrid probe (detection limit 95 ng mL-1). Fluorescence imaging in PC12 cell lines demonstrated that the BSA-AuNCs could be utilized in visualization assay towards intracellular DBH. Additionally, the sensors were tested in a real matrix by spiking serum samples with satisfactory recoveries.

A novel synthesis of new antibacterial nanostructures based on Zn-MOF compound: design, characterization and a high performance application.

In this study, the novel zinc metal-organic frameworks (MOF) nanostructure has been employed, which was developed using an affordable, environmental friendly, efficient and fast method of ultrasound-assisted reverse micelle (UARM). These nanostructures were identified with various techniques such as FT-IR, XRD, BET, SEM, TG-DSC, TEM and EDS. It was found that the Zn-MOF samples have favorable physicochemical properties. The impact of experimental parameters of the UARM method is effective on the resulting properties, such as high surface area of the products that increases the interactions between the Zn-MOF nanostructure and bacteria.Their antibacterial activities were investigated using diffusion methods in agar and also with dilutions of Zn-MOF samples. Antibiotics (tetracycline and ampicillin) and their anti-biofilm effects were evaluated using microplate method. Obtained results revealed that the Zn-MOF nanostructures have high antibacterial properties which, could be due to the nature of the applied Zn-MOF as well as the optimization process. The Zn- MOF nanostructures could be a novel antibacterial material as biocatalyst processes.

Evaluating the photodynamic therapy efficacy using 5-aminolevulinic acid and folic acid-conjugated bismuth oxide nanoparticles on human nasopharyngeal carcinoma cell line.

Selective accumulation of photosensitizers (PSs) into cancerous cells is one of the most important factors affecting photodynamic therapy (PDT) efficacy. 5-Aminolevulinic acid (5-ALA) is precursor of a strong PS, protoporphyrin-IX (Pp-IX); but it has poor permeability in lipophilic membrane of the cells due to its hydrophilic property. Therefore, establishment of an improved delivery strategy could highly affect on treatment outcome. Moreover, folate receptors (FRs) are overexpressed on the surface of many tumor cells. In the present work, targeting ligand folic acid (FA) and 5-ALA conjugated bismuth oxide nanoparticles (FA-5ALA-Bi2O3 NPs) were synthesized; and used in PDT against human nasopharyngeal carcinoma cells (KB cell line). The KB cells incubated with the synthesized NPs for 2 h; then illuminated using a custom-made red light LED lamp at the light dose of 26 J/cm2. MTT and caspase-3 activity assays were performed to evaluate the efficacy of treatment. Results showed that FR targeting ligand enables selective endocytosis of FA-5-ALA-conjugated NPs into KB cells. Improved internalization of 5-ALA into cells decreased the cell viability to about 50%, 65%, and 85% in the groups receiving FA-5ALA-Bi2O3 NPs, 5ALA-Bi2O3 NPs, free 5-ALA and subsequent PDT, respectively. Therefore, FA-5ALA-Bi2O3 NPs can significantly increase the cell killing effect of PDT.

In vitro outlook of gold nanoparticles in photo-thermal therapy: a literature review.

Hyperthermia is an anti-cancer treatment in which the temperature of the malignant tumor is increased more than other adjacent normal tissues. Microwave, ultrasound, laser, and radiofrequency sources have been used for hyperthermia of cancerous tissues. In the past decade, near-infrared (NIR) laser for cancer therapy, known as photo-thermal therapy (PTT), was expanded in which the photo-sensitizer agent converts the light photon energy to heat. The heat following PTT can destroy cancer cells. There are some photo-sensitizer agents which have been used for PTT; however, owing to recent advances in nanotechnology, noble metal nanoparticles like gold (Au) nanoparticles (GNPs) have been used successfully in PTT. GNPs have some desirable specifications, including simple and controlled synthesis, small size, high level of biocompatibility, and surface plasmon resonance (SPR). The SPR effect of the GNPs increases the radiative properties like absorption and scattering; therefore, they can be used in PTT. In this article, we reviewed recent in vitro studies of PTT using GNPs in literature. At first, we focus on the physical properties of GNPs, their interaction with infrared radiation, and physical parameters governing the interaction of infrared radiation with the GNPs. Then, we review the passive and active targeting of GNPs using the different coating to induce the thermal damage in cancer cells using low-level laser PPT. The GNPs' cellular internalization into cancer cells is a challenge which is consequently considered. In this review, we also summarize the results of synergistic cancer therapy studies on the combination of radiation therapy as a routine cancer treatment and PTT: in which significant improvement occurs in treatment efficacy.

Investigating the Cytotoxicity of Folate-Conjugated Bismuth Oxide Nanoparticles on KB and A549 Cell Lines.

Purpose: Lately, bismuth-based nanomaterials have been widely utilized in medical researches such as imaging, drug delivery and radio-sensitization. Despite their advantages, bismuth-based compounds have shown toxic effects in humans. There are few studies on cytotoxicity effects of bismuth oxide (Bi2O3) nanoparticles (NPs) in-vitro. In this study, we aimed to investigate cytotoxicity of bare and also folate and 5-aminolevulinic acid (5-ALA)-conjugated Bi2O3 NPs on nasopharyngeal carcinoma (KB) and lung cancer (A549) cell lines. Methods: Bi2O3 NPs were synthesized and conjugated with folate and 5-ALA. KB and A549 cells were cultured and incubated with 10, 20, 50 and 100 µg/ml concentrations of bare and folate-5-ALA-conjugated NPs. The survival rates were obtained after 2 and 24 hours incubation of the cells with NPs using MTT assay. Also, apoptosis and ROS generation induced by the NPs in the treated cells were obtained using Caspases-3 activity assay and flow cytometry analysis, respectively. Results: Bi2O3 NPs were successfully synthesized with average size of 19.2 ± 6.5 nm, then conjugated with 5-ALA and folate. Either naked or folate-conjugated NPs were easily taken up by the cells in a concentration-dependent manner and showed cytotoxic effects. The significant cell death was noted at the concentrations more than 50 µg/ml for both compounds. Conclusion: Results indicated low cytotoxicity of the prepared NPs at lower incubation periods, which is very important for their further applications. However, 24 hours incubation of the cells with both forms of NPs caused more cell killing and the cytotoxicity increased with increasing concentrations of the NPs.