Firat Baris Barlas

Gold nanoparticle loaded phytosomal systems: synthesis, characterization and in vitro investigations

Most medicinal and pharmaceutical herbal extracts are poorly soluble in aqueous moieties and have reduced adsorption by living cells. Liposomal encapsulation of those so called phytosomes could be a solution to overcome this problem. Meanwhile, much research shows that metallic nanoparticles such as gold nanoparticles (AuNPs) exhibit biological activity such as wound healing and antioxidant properties on living cells. Here, we constructed a novel liposomal formulation by encapsulating both Calendula officinalis extract and AuNPs. After the preparation of vesicles using the traditional thin film hydration method within extrusion, the resulting AuNP–phytosomes were characterized by dynamic light scattering size measurements, zeta potential and atomic force microscopy. These vesicles are less than 100 nm in size and have a high encapsulation efficiency for chlorogenic acid and quercetin as the model major molecules of Calendula extract. Furthermore, AuNP–phytosomes exhibited antioxidant and wound healing activity significantly according to the free forms of each encapsulated material and the plain liposome as well as the phytosome form. Moreover, the cellular interactions of the vesicles were monitored using the nano-vesicles prepared by Texas-Red labelled lipids under fluorescence microscopy.

Polymeric Thioxanthones as Potential Anticancer and Radiotherapy Agents

Thioxanthone (TX) and its derivatives, which are widely used as photoinitiators in UV curing technology, hold promising research interest in biological applications. In particular, the use of TXs as anticancer agent has recently been manifested as an outstanding additional property of this class of molecules. Incorporation of TX molecules into specially designed polymers widens their practical use in such applications. In this study, two water-soluble, biocompatible, and stable polymers, namely poly(vinyl alcohol) and poly(ethylene glycol), possessing TX moieties at the side chains and chain ends, respectively, are prepared and used as anticancer and radiotherapy agents. The findings confirm that both polymers are potential candidates for therapeutic agents as they possess useful features including water-solubility, radiosensitizer effect, and anticancer activity in a polymeric scaffold.

Poly(p-phenylene) with Poly(ethylene glycol) Chains and Amino Groups as a Functional Platform for Controlled Drug Release and Radiotherapy

Conventional cancer treatments such as chemotherapy, radiotherapy, or combination of these two result in side effects, which lower the quality of life of the patients. To overcome problems with these methods, altering the drug properties by conjugating them to carrier polymers has emerged. Such polymeric carriers also hold the potential to make tumor cells more sensitive to radiation therapy. Herein, poly(p-phenylene) (PPP) polymer with poly(ethylene glycol) (PEG) chains and primary amino groups (PPP-NH2 -g-PEG) is synthesized and conjugated with anticancer drug Doxorubicin (DOX). pH dependent drug release experiments are performed at pH 5.3 and pH 7.4, respectively. Cell viability studies on human cervix adenocarcinoma cells show that lower doses of DOX inhibit cell proliferation when conjugated with nontoxic doses of PPP-NH2 -g-PEG polymer. Additionally, PPP-NH2 -g-PEG/Cys/DOX bioconjugate significantly increases radiosensitive properties of DOX. It is possible to use lower doses of DOX when conjugated to PPP-NH2 -g-PEG in combination with radiotherapy.

A novel DAD type and folic acid conjugated fluorescent monomer as a targeting probe for imaging of folate receptor overexpressed cells

We describe a modification and post‐functionalization technique for a donor–acceptor–donor type monomer; 6‐(4,7‐bis(2,3‐dihydrothieno[3,4‐b][1,4]dioxin‐5‐yl)‐2H‐benzo[d][1,2, 3]triazol‐2‐yl)hexan‐1‐amine. Folic acid was attached to the fluorescent structure. The conjugation was confirmed via NMR and Fourier transform infrared analyses. Cytotoxicity was investigated and the comparison of association of targeted monomeric structures in tumor cells was monitored via fluorescence microscopy.

Novel glyconanoconjugates: synthesis, characterization and bioapplications

The impressive properties of nanoparticles (NPs) have caused them to gain considerable attention for biological applications such as cancer therapy. Among the many nanoparticles used in the treatment of cancer, carbohydrate derivatized modified NPs lead the way with enhanced internalization and therapy efficacy for cancerous cell lines. In this research, an aminochlorase Schiff base, which can be beneficial as a therapy material, with a galactose residue was used as a potentially active modifier. Gold and silver nanoparticles (AuNPs and AgNPs) can be readily modified with a sugar Schiff base ligand (1) by using cysteamine hydrochloride residues as a linker between the nanoparticle surface and the ligand. The resulting glyco-nanoparticles were characterized using transmission electron microscopy, X-ray photoelectron microscopy and spectrophotometric techniques. Additionally, this modification type within a galactose derived Schiff base is the first work with a bioapplication, especially in radiotherapy. For further biological applications in cancerous cell lines, two commonly used cell lines, human cervix adenocarcinoma (HeLa) and human lung carcinoma cell line (A549) were introduced into the biological evaluation of those NP–ligand conjugates and satisfactory radioactivity results were obtained because of the radiosensitizing effect of the AuNPs and AgNPs.

Bioconjugation and Applications of Amino Functional Fluorescence Polymers

Synthesis and novel applications of biofunctional polymers for diagnosis and therapy are promising area involving various research domains. Herein, three fluorescent polymers, poly(p-phenylene-co-thiophene), poly(p-phenylene), and polythiophene with amino groups (PPT-NH2 , PPP-NH2 , and PT-NH2 , respectively) are synthesized and investigated for cancer cell targeted imaging, drug delivery, and radiotherapy. Polymers are conjugated to anti-HER2 antibody for targeted imaging studies in nontoxic concentrations. Three cell lines (A549, Vero, and HeLa) with different expression levels of HER2 are used. In a model of HER2 expressing cell line (A549), radiotherapy experiments are carried out and results show that all three polymers increase the efficacy of radiotherapy. This effect is even more increased when conjugated to anti-HER2. In the second part of this work, one of the selected polymers (PT-NH2 ) is conjugated with a drug model; methotrexate via pH responsive hydrazone linkage and a drug carrier property of PT-NH2 is demonstrated on neuroblastoma (SH-SY5Y) cell model. Our results indicate that, PPT-NH2 , PPP-NH2 , and PT-NH2 have a great potential as biomaterials for various bioapplications in cancer research.

A multi-functional fluorescent scaffold as a multi-colour probe: design and application in targeted cell imaging

A novel scaffold material based on a novel targeting strategy has been developed, benefiting from recent progress in the development of fluorescent bioprobes. This concept suggests that several specifications which are desired for cancer cell targeting and imaging studies can be satisfied at the same time in one multifunctional scaffold. Besides, such scaffolds exhibit multi-colour properties when combined with a targeting moiety. For this purpose, a fluorescent and functional monomer, 3-(1H-phenanthro[9,10-d]imidazol-2-yl)phenol (PIP) and an antibody labelling kit (CF555) were merged on the same scaffold to generate the proposed bioprobe. This design offers multicolour cell images by emitting at dual wavelengths with no quenching in its fluorescent property. Also, pendant alcohol groups in the structure of PIP enable covalent attachment to labelled protein, CF555/anti-CD44 in order to enhance the biological activity and specificity towards the target. After combining with the targeting moiety, the bioconjugate was characterized, tested for in vitro studies, and the cellular internalization was monitored in live cells via the fluorescence microscope technique. The present work with such a strategy explores the potential use of the proposed fluorescent probe for the first time. The aim is to achieve targeted imaging of CD44 positive U87-MG cancer cells and determine specific cellular labelling via fluorescence imaging and flow cytometry experiments.