E. Ilker Medine

The synthesis and targeting of PPP-type copolymers to breast cancer cells: Multifunctional platforms for imaging and diagnosis

Herein, we demonstrate the synthesis and application of water-soluble, biomolecule conjugated PPP copolymers bearing poly(ethylene glycol) (PEG) side chains as fluorescent probes for the in vitro imaging of cancer cells. The targeting of fluorescent polymers to breast cancer cells allows effective visualization and discrimination of MCF7 cells from human mammary epithelial cells. Furthermore, these materials are also suitable for efficient radiolabeling via125I which enables dual-modality holding the possibility of both radioactive and fluorescence imaging in cancer diagnosis applications.

Affinity Based Laccase Immobilization on Modified Magnetic Nanoparticles: Biosensing Platform for the Monitoring of Phenolic Compounds

The authors report an electrochemical phenol biosensor based on the immobilization of laccase (Lac) on the surface of copper capped magnetic core–shell (Fe3O4–SiO2) nanoparticles (MNPs). After synthesis, MNP surfaces were functionalized by silanization and then, modified with histidine (His) and copper, respectively. The performance of the MNP-His/Cu/Lac biosensor has been investigated at −0.05 V versus Ag/AgCl. The proposed biosensor allowed to detect catechol and phenol in the range of 0.01–0.4 mM and 0.025–0.2 mM, respectively. Finally, phenol analysis in culture medium of P. putida adapted to phenol was successfully demonstrated with appreciable recovery values. GRAPHICAL ABSTRACT

Enzymatic synthesis of 125/131I labeled 8-hydroxyquinoline glucuronide and in vitro/in vivo evaluation of biological influence

8-Hydroxyquinoline (8-OHQ) is a long-known molecule which due to its metal-complexation ability is frequently used for analysis. It is also called oxine. Oxine and derivatives have been investigated to process antitumor and antimicrobial activities. 8-Hydroxyquinolyl-glucuronide (8-OHQ-Glu) was enzymatically synthesized using microsome preparates separated from Hutu-80 cells, labeled with (125)I to perform a radionuclide labeled prodrug and investigated of its biological affinities on Hutu-80 (human duodenum intestinal adenocarcinoma), Caco-2 (human colorectal adenocarcinoma), Detroit 562 (human pharynx adenocarcinoma) cells and ACBRI 519 (primary human small intestine epithelial cells) in this work. UDP-glucuronyl transferase (UDPGT) rich microsome preparates, which are used for glucuronidation in enzymatic synthesis, were extracted from Hutu-80 cells. 8-OHQ-Glu components were labeled using iodogen method with (125)I and (131)I. Structural analyses were performed with LC/MS/MS, (1)H NMR and (13)C-MMR for identify and measure chemical constituents. Results confirmed expected molecular structure. 8-OHQ-Glu could successfully radioiodinated with (125/131)I according to iodogen method. (125)I-8-OHQ-glucuronide incorporated with human gastrointestinal cancer cells such as Detroit-562 (human pharynx adenocarcinoma) (12.6%), Caco-2 (human colorectal adenocarcinoma) (7.8%), Hutu- 80 (human duodenum intestinal adenocarcinoma) (9.5%) and ACBRI 519 (primary human small intestine epithelial cells) (6.40%). (131)I-8-OHQ-Glu was tested in mice bearing subcutaneously implanted Caco-2 colorectal adenocarcinoma cells. The results demonstrated that radioiodinated 8-OHQ-Glu may be promising anticancer prodrug.

Synthesis, radiolabeling and in vivo biodistribution of diethylstilbestrol phosphate derivative (DES-P)

Diethylstilbestrol (DES) is a well known, nonsteroidal estrogen with high affinity for the estrogen receptor (ER). Today DES is used to treat breast and prostate cancers. A phosphate derivative of DES [Diethylstilbestrol diphosphate (DES-P)] which is specific to tumor cells consisting alkaline phosphatase enzyme was synthesized and labeled with 99mTc using tin chloride as reducing agent. In vivo biological activity of 99mTc labeled diethylstilbestrol phosphate compound (99mTc-DES-P) was examined by biodistribution studies on Wistar Albino rats. Statistical evaluation was performed using SPSS 13 program. The percentage (%) radiolabeling yield of 99mTc-DES-P and quality control studies were done by Thin Layer Radio Chromatography (TLRC). Results showed that, 99mTc-DES-P may be proposed as an imaging agent for ER enriched tumors such as uterus and prostate and their metastases in bones.

Radioiodinated Magnetic Nanoparticles Conjugated With Moxifloxacin: Synthesis and In Vitro Biological Affinities

Magnetic nanoparticles (MNPs) were synthesized and coated with tetraethyl orthosilicate and aminosilane to create functional amino groups. Moxifloxacin (MXF) was conjugated to the modified MNPs using glutaraldehyde as crosslinker. Finally, MXF conjugated magnetic nanoparticles were radiolabeled and their biological affinities such as cell incorporation ratio, cytotoxicity, and their potential as cell imaging probe were investigated using A-549 cells. GRAPHICAL ABSTRACT

Synthesis, characterization and radiolabeling of folic acid modified nanostructured lipid carriers as a contrast agent and drug delivery system

Nanostructured lipid carriers (NLCs) are the new generation of solid lipid drug delivery systems. Their suitability as contrast agents for gamma scintigraphy is an attracting major attention. The aim of current study was to prepare surface modified nanostructured lipid carrier system for paclitaxel (PTX) with active targeting and imaging functions. In accordance with the purpose of study, PTX loaded nanostructured lipid carriers (NLCs) prepared, modified with a folate derivative and radiolabeled with technetium-99m tricarbonyl complex (99mTc(CO)3+). Cellular incorporation ratios of radiolabeled nanoparticles (99mTc(CO)3-PTX-NLC) were investigated in vitro on three cancer cell lines. Additionally in vivo animal studies conducted to evaluate biological behavior of 99mTc(CO)3-PTX-NLC on female Wistar Albino rats. Biodistribution results showed that the folate derivative modified 99mTc(CO)3-PTX-NLC had considerably higher uptake in folate receptor positive organs. The data obtained from present study could be useful in the design of biodegradable drug carriers of PTX and folate receptor based tumor imaging agents.

Radioiodine labeled CdSe/CdS quantum dots: Lectin targeted dual probes

Abstract CdSe/CdS quantum dots (QD) were synthesized and bioconjugated with Sambucus nigra agglutinin (SNA) lectin (Lec). Mannose triflate and cysteamine molecules (MTC) were also utilized to prepare MTC-QDs and MTC-QDs-Lec probes as well as Lec bound QDs. Afterwards; potential use of these nanoparticles as radiolabeled fluorescence nano-probes for the cell imaging studies has been investigated. Biological activities of 125I–, 125I-MTC-QDs, MTC-QDs- Lec-125I, QDs-Lec-125I and Lec-125I were examined on various cancer cell lines such as Caco-2, MCF-7 and A-549 in terms of cell incorporation. QDs-Lec-125I exhibited the highest cell incorporation on whole cell lines. In addition, the QDs-Lec-131I, was used for in vivo imaging. The whole body distribution of the radiolabeled QDs on New Zealand rabbits and Balb C mice were examined by taking dynamic and static images. Radioactivity cleared from the kidneys and the bladder, while significant amount radioactivity was retained in the heart and liver within 24 h.

Isolation and Immobilization of His-Tagged Alcohol Dehydrogenase on Magnetic Nanoparticles in One Step: Application as Biosensor Platform

His-tagged Alcohol dehydrogenase was produced as a recombinant protein in E. coli. Afterwards, isolation and immobilization of the enzyme was carried in one-step via copper modified magnetic nanoparticles (MNPs) by the effect of interactions between Cu and histidine. The resulting enzyme bound MNPs was then attached to the surface of carbon paste electrode by the magnetic force and used as an electrochemical biosensor for the alcohol sensing applications.

PLGA encapsulation effect on Bioquin-HMPAO: radiolabeling and in vitro behaviour on brain and lung cancer cells

Bioquin-HMPAO (BH) was previously investigated as a novel brain imaging agent by in vivo biodistribution studies. Present studies are carried out to explore radiolabeling and in vitro behaviour evaluation of poly (lactic-co-glycolic acid) (PLGA) encapsulated BH nanocapsules (BH-PLGA NCs). BH-PLGA NCs were characterized utilizing dynamic light scattering and scanning electron microscope. Encapsulation effect on radiolabeling with 99mTc was examined by stability and lipophilicity studies and effect on in vitro behaviour of 99mTc-BH was evaluated by incorporation studies on DAOY, U87-MG and A549 cells. It is observed that PLGA encapsulation has a positive and reinforcement effect.

PLGA encapsulation and radioiodination of indole-3-carbinol: investigation of anticancerogenic effects against MCF7, Caco2 and PC3 cells by in vitro assays

Encapsulation with PLGA of I3C and radioiodination have been performed. Anticancerogenic effects of I3C and I3C-PLGA have been investigated utilizing in vitro methods on breast adenocarcinoma epithelial (MCF7), colon adenocarcinoma epithelial (Caco2), prostate carcinoma epithelial (PC3) cells. Characterization of I3C-PLGA have been performed with DLS method and SEM analysis. I3C and I3C-PLGA compounds have been radiolabeled in high yields with 131I which is widely used for diagnosis and treatment in Nuclear Medicine. All experimental results demonstrated that radioiodinated compounds are promising in order to be used in Nuclear Medicine as well as present study contributed previously reported studies.