Synthesis and Optimization of the Docetaxel-Loaded and Durvalumab-Targeted Human Serum Albumin Nanoparticles, In Vitro Characterization on Triple-Negative Breast Cancer Cells.

Triple-negative breast cancer (TNBC) tends to behave more aggressively compared to other breast cancer subtypes due to the lack of receptors and its limited targeting therapy. In recent years, nanotechnology advancement has led to the development of various nanoparticle platforms for the targeted treatment of cancers. Especially, HSA-NPs have specific advantages such as biocompatibility, adjustable size during production, and relatively easy synthesis. In this study, HSA-NPs were encapsulated with docetaxel (DTX) and functionalized with polyethylene glycol (PEG), also becoming a targeting nanoplatform modified with durvalumab (DVL), and the whole nanostructure was well characterized. Subsequently, drug release studies and various in vitro cell culture studies such as determining the cytotoxicity and apoptotic levels of the nanoplatforms and PD-L1 using ELISA test were conducted on MDA-MB-468, MDA-MB-231, and MCF-7 cells. According to the results, HSA-DTX@PEG-DVL NPs showed better cytotoxicity compared to DTX in all the three cell lines. In addition, it was observed that the HSA-DTX@PEG-DVL NPs did not lead the cells to late apoptosis but were effective in the early apoptotic stage. Moreover, the ELISA data showed a significantly induced PD-L1 expression due to the presence of DVL in the nanostructure, which indicates that DVL antibodies successfully bind to the HSA-DTX@PEG-DVL nanostructure.

Chemo-Photothermal Combination Therapy of HER-2 Overexpressing Breast Cancer Cells with Dual-Ordered Mesoporous Carbon@Silica Nanocomposite.

In cancer treatment, the complexity of tumors seriously affects the therapeutic potential of the treatment. Treatments with combination therapy result in more potent effects than monotherapy or their theoretical combination in cancer treatment. Photothermal therapy (PTT) includes applying phototherapeutic agents that cause local hyperthermia responsible for the thermal ablation of tumor cells after applying near-infrared light and is often applied with other combination therapies. In this study, the chemo-PTT potential of synthesized drug-loaded and targeted GEM/TRA-MC@Si nanocomposite on Her2 positive breast cancer cell line (SK-BR-3) and human triple-negative breast cancer cell line (MDA-MB-231) was investigated using NIR application as in vitro. First, the cell viability (IC50) value of the GEM/TRA-MC@Si nanocomposite was determined as 25 µg/µL. Then, chemo-PTT was performed, and the viability of the cells was evaluated. In addition, the live/dead cell rate was established by staining with the Calcein-AM and EthD-1, and apoptosis tests were completed. When the surface temperature of Her2 positive SK-BR-3 cells exceeded 47 °C during PTT with an irradiation time of > 100 s, it caused cell death. In this study, it was demonstrated that in vitro PTT (1 W/cm2, 180 s) was applied using GEM/TRA-MC@Si nanocomposite (25 µg/mL) on her2 + SK-BR-3 cell line, which contributed to the reduction of cell viability. In addition, this study demonstrates that chemo-PTT with targeted GEM/TRA-MC@Si nanocomposite induced SK-BR-3 cell viability and can initiate cell death through the apoptosis pathway under optimized irradiation conditions. Herewith chemo-PTT combination therapy of targeted GEM-TRA/MC@Si nanocomposite was found to be effective on SK-BR-3 cells as in vitro.

Development of antimicrobial nanocomposite scaffolds via loading CZTSe quantum dots for wound dressing applications.

The antimicrobial properties of scaffolds designed for use in wound healing are accepted as an important factor in the healing process to accelerate the wound healing process without causing inflammation. For this purpose, chitosan-polyvinyl alcohol composite membranes loaded with Cu2ZnSnSe4quantum dots (CZTSe QDs) as an antibacterial and cytocompatible biomaterial to regulate the wound healing process were produced. CZTSe QDs particles were synthesized under hydrothermal conditions. Polymer-based nanocomposites with different concentrations of the synthesized nanoparticles were produced by the solvent casting method. After detailed physicochemical and morphological characterizations of CZTSe QDs and composite membranes, antibacterial activities and cell viability were extensively investigated against gram-positive and gram-negative bacterial and yeast strains, and L929 mouse fibroblast cells lines, respectively. The results show that the preparation of composite scaffolds at a QDs concentration of 3.3% by weight has the best antimicrobial activity. Composite scaffold membranes, which can be obtained as a result of an easy production process, are thought to have great potential applications in tissue engineering as wound dressing material due to their high mechanical properties, wettability, strong antibacterial properties and non-toxicity.

Imaging and detection of cell apoptosis byIn vitrophotodynamic therapy applications of zinc (II) phthalocyanine on human melanoma cancer.

This study aims to investigate the photodynamic therapy (PDT) effects on MeWo (human melanoma cells) and HaCaT (normal human keratinocyte cells) by light stimulation of different concentrations of Zinc (II)-tetra-tert-butyl-phthalocyaninato (ZnPc). MTT viability assay data indicated that a 25 µM concentration of ZnPc is cytotoxic to the melanoma cancer cells while this concentration of ZnPc is not cytotoxic for the HaCaT cell line. Moreover, the results showed that photoactivated ZnPc at 12.5 µM concentration reduced the cell viability of the MeWo cell line to about 50 %. At this photosensitizing concentration, the efficacy of light doses of 20, 30, 40, and 50 J/cm2 was evaluated against MeWo and HaCaT cells. ZnPc at a concentration of 12.5 µM activated with a light dose of 50 J/cm2 was the most efficient for the killing of MeWo cells. In conclusion, the 12.5 µM of ZnPc with the treatment light dose of 50 J/cm2 from a RED light source was adequate to destroy MeWo cells by the ROS-induced apoptosis mechanism. It also exhibited low killing effects on healthy HaCaT cells. These findings are supported by the results of apoptosis with the Annexin V & Dead Cell Kit and fluorescence imaging.

In vitro evaluation of 99m Tc-sultamicillin for infection imaging.

Early detection of the site of infection non-invasively with radiolabeled molecules is important for the success of treatment. Technetium-99m labeled antibiotics have the potential to discriminate between bacterial infection and sterile inflammation. Sultamicillin is the tosylate salt of the double ester of sulbactam plus ampicillin. In this study, sultamicillin was labeled with 99m Tc according to the stannous chloride method. Quality control studies of radiolabeled sultamicillin were performed by radiochromatographic methods. In vitro binding assays were performed in live and heat-killed gram-positive Staphylococcus aureus and gram-negative Escherichia coli strains. The radiolabeling yield of 99m Tc-sultamicillin was determined as 97.8% ± 3.1% (n = 5). The maximum bacterial uptake of 99m Tc-sultamicillin was 80.7% ± 11.00% at 4 h for living S. aureus and 93.2% ± 4.40% at 2 h for E. coli. Bacterial uptake study results show that sultamicillin has the potential to be a nuclear imaging agent, especially in infections caused by gram-negative E. coli and gram-positive S. aureus.

Evaluation of 99mTechnetium-Vancomycin Imaging Potential in Experimental Rat Model for the Diagnosis of Infective Endocarditis.

BACKGROUND: Infective endocarditis (IE) is an infection of the heart's endocardial surface. In recent years, nuclear imaging methods have gained importance in the diagnosis of IE. The present study aims to investigate the imaging potential of 99mTc-labeled vancomycin (99mTc-Vancomycin) as a new agent that would enable the diagnosis of IE in its early stages when it is difficult to diagnose or has small vegetation in the experimental rat model. METHODS: 99mTc-Vancomycin scintigraphy was evaluated for its accumulation in IE with Staphylococcus aureus performed in an experimental rat model. Serial planar scintigraphic and biodistribution analysis of infected vegetations are compared to rats with sterile vegetations. The heart was identified as an infected organ, the liver was identified as a non-infected organ and the heart/liver uptake ratio (T / NT ratio) was compared between infective endocarditis and sterile endocarditis groups. RESULTS: Planar scintigrams (in vivo measurements) showed more uptake in the heart of rats in the infective endocarditis group compared to the uptake in the heart of rats in the sterile endocarditis group, but this difference was not statistically significant (p>0.05). From the ex vivo measurements, the 99mTc-Vancomycin heart uptake increased significantly (p = 0.016), liver uptake was significantly decreased (p = 0.045) and the T/NT ratio was significantly higher (p = 0.014) in the infective endocarditis group compared to the sterile endocarditis group. CONCLUSION: In this experimental study, 99mTc-Vancomycin scintigraphy ensured the detection of ex vivo infected tissue in a rat model of IE. In addition, the absence of significant 99mTc-Vancomycin uptake in the sterile endocarditis group indicates that this agent targeted the infected tissue instead of the sterile inflammatory tissue. Finally, this agent should also be evaluated with animal- specific imaging devices.

Radiolabeling, In Vitro Cell Uptake, and In Vivo Photodynamic Therapy Potential of Targeted Mesoporous Silica Nanoparticles Containing Zinc Phthalocyanine.

Photodynamic therapy (PDT) is a noninvasive therapy based on the photodynamic effect. In this study, we sought to determine intracellular uptake and in vivo photodynamic therapy potential of Zn phthalocyanine-loaded mesoporous silica nanoparticles (MSNP5) against pancreatic cancer cells. MSNP5 were labeled with 131I; the radiolabeling efficiency was found to 95.5 ± 1.2% in pH 9 and 60 min reaction time. Besides, the highest intracellular uptake yields of 131I-MSNP5 nanoparticles in MIA PaCa-2, AsPC-1, and PANC-1 cells were determined as 43.9 ± 3.8%, 41.8 ± 0.2%, and 37.9 ± 1.3%, respectively, at 24 h incubation time. In vivo PDT studies were performed with subcutaneous xenograft cancer model nude mice with AsPC-1 pancreatic cancer cells. For photodynamic therapy, 685 nm red laser light 100 J/cm2 light dose using and 5-20 µM ZnPc containing MSNP5 concentrations were applied. Histopathological studies revealed that the ratio of necrosis in tumor tissue was higher in the treatment group than the control groups.

Antifungal photodynamic activities of phthalocyanine derivatives on Candida albicans.

Antimicrobial resistance is one of the most important causes of morbidity and mortality in the treatment of infectious diseases worldwide. Candida albicans is one of the most virulent and common species of fungi to cause invasive fungal infections on humans. Alternative treatment strategies, including photodynamic therapy, are needed for controlling these infectious diseases. The aim of this study was to investigate the antifungal photodynamic activities of phthalocyanine derivatives on C. albicans. The minimum inhibitory concentration (MIC) values of compounds were determined by the broth microdilution method. Uptake of the compounds in C. albicans and dark toxicity of the compounds were also investigated. Photodynamic inhibition of growth experiments was performed by measuring the colony-forming unit/mL (CFU/mL) of the strain. Maximum uptake into the cells was observed in the presence of 64 µg/mL concentration for each compound except for ZnPc. Compounds did not show dark toxicity/inhibitory effects at sub-MIC concentrations on C. albicans when compared to the negative control groups. Zn(II)Pc, ZnPc, and ZnPc-TiO2 showed fungicidal effect after irradiation with the light dose of 90 J/cm2 in the presence of the compounds. In addition to the fungicidal effects, SubPc, SubPc-TiO2, Es-SiPc, and Es-SubPc compounds were also found to have inhibitory effects on the growth of yeast cells after irradiation.

Synthesis of new water-soluble ionic liquids and their antibacterial profile against gram-positive and gram-negative bacteria.

A series of imidazolium bromide salts (NIM-Br 1a, 1b and 1c) bearing different lengths of alkyl chains were synthesized and theirin vitro antibacterial activities were determined by measuring the minimum inhibitory concentration (MIC) values for Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Enterococcus faecalis. In addition, these imidazolium derivatives were also evaluated against biofilm produced by these bacterial strains. All compounds were found to be effective against Gram-positive and Gram-negative bacteria, and also more effective on the S. aureus biofilm production than the others.

Malignant transformation arising from mature cystic teratoma of the ovary: a report of six cases.

AIM: Malignant transformation of mature cystic teratoma (MCT) is an uncommon complication. Preoperative diagnosis is difficult because of the lack of specific symptoms and signs indicating malignancy. Thus, we retrospectively analyzed the clinical characteristics of patients and the role of surgery in their management. MATERIAL AND METHODS: During a 9-year period (2002-2010), six patients with malignant transformation arising from ovarian MCT were treated at the Gynecologic Oncology Unit of Bakirkoy Woman and Children's Training and Research Hospital. A retrospective chart review and analysis of the patients' data were conducted. RESULTS: Malignant transformation arising from ovarian MCT accounted for 1.9% of all ovarian MCT (6/321). Three cases were stage IA and the other three were stage IC. Histologically, three of six cases had squamous cell carcinoma (50%), two had a carcinoid tumor (33%), and one had mucinous adenocarcinoma (17%). All patients underwent comprehensive surgical staging. Two patients received adjuvant chemotherapy and one received adjuvant chemoradiation. Five of six patients were observed for 16-104 months and no recurrence was detected. One patient with a carcinoid tumor in stage IC died of disease within 34 months following the surgery. CONCLUSION: Early detection of malignant transformation arising from MCT is mandatory for treating patients, but in most patients malignancy was detected intraoperatively. Surgical cytoreduction with a complete staging procedure and adjuvant treatment may be reasonable for stage IC. Additionally, prognosis is better when the tumor is completely excised and does not extend beyond the capsule.