Ozge Kozgus Guldu

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

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

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.

An in-vivo pilot study into the effects of FDG-mNP in cancer in mice

Purpose Previously, fluorodeoxy glucose conjugated magnetite nanoparticles (FDG-mNPs) injected into cancer cells in conjunction with the application of magnetic hyperthermia have shown promise in new FDG-mNPs applications. The aim of this study was to determine potential toxic or unwanted effects involving both tumour cells and normal tissue in other organs when FDG-mNPs are administered intravenously or intratumourally in mice. Materials and methods FDG-mNPs were synthesized. A group of six prostate-tumour bearing mice were injected with 23.42 mg/ml FDG-mNPs (intravenous injection, n = 3; intratumoural injection into the prostate tumour, n = 3). Mice were euthanized and histological sampling of tissue was conducted for the prostate tumour, as well as for lungs, lymph nodes, liver, kidneys, spleen, and brain, at 1 hour (n = 2) and 7 days (n = 4) post-injection. A second group of two normal (non-cancerous) mice received the same injection intravenously into the tail vein and were euthanised at 3 and 6 months post-injection, respectively, to investigate if FDG-mNPs remained in organs at those time points. Results In prostate-tumour bearing mice, FDG-mNPs concentrated in the prostate tumour, while relatively small amounts were found in the organs of other tissues, particularly the spleen and the liver; FDG-mNP concentrations decreased over time in all tissues. In normal mice, no detrimental effects were found in either mouse at 3 or 6 months. Conclusion Intravenous or intratumoural FDG-mNPs can be safely administered for effective cancer cell destruction. Further research on the clinical utility of FDG-mNPs will be conducted by applying hyperthermia in conjunction with FDG-mNPs in mice.

Tissue morphology and gene expression characterisation of transplantable adenocarcinoma bearing mice exposed to fluorodeoxyglucose-conjugated magnetic nanoparticles

Fluorodeoxyglucose-conjugated magnetic nanoparticles, designed to target cancer cells with high specificity when heated by an alternating magnetic field, could provide a low-cost, non-toxic treatment for cancer. However, it is essential that the in vivo impacts of such technologies on both tumour and healthy tissues are characterised fully. Profiling tissue gene expression by semi-quantitative reverse transcriptase real-time PCR can provide a sensitive measurement of tissue response to treatment. However, the accuracy of such analyses is dependent on the selection of stable reference genes. In this study, we determined the impact of fluorodeoxyglucose-conjugated magnetic nanoparticles on tumour and non-tumour tissue gene expression and morphology in MAC16 adenocarcinoma established male NMRI mice. Mice received an injection of 8 mg/kg body weight fluorodeoxyglucose-conjugated magnetic nanoparticles either intravenously in to the tail vein, directly into the tumour or subcutaneously directly overlying the tumour. Tissues from mice were sampled between 70 minutes and 12 hours post injection. Using the bioinformatic geNorm tool, we established the stability of six candidate reference genes (Hprt, Pgk1, Ppib, Sdha, Tbp and Tuba); we observed Pgk1 and Ppib to be the most stable. We then characterised the expression profiles of several apoptosis genes of interest in our adenocarcinoma samples, observing differential expression in response to mode of administration and exposure duration. Using histological assessment and fluorescent TUNNEL staining, we observed no detrimental impact on either tumour or non-tumour tissue morphology or levels of apoptosis. These observations define the underlying efficacy of fluorodeoxyglucose-conjugated magnetic nanoparticles on tumour and non-tumour tissue morphology and gene expression, setting the basis for future studies.

A novel theranostic nanobioconjugate: 125/131I labeled phenylalanine conjugated boron nitride nanotubes

Here we report the synthesis of boron nitride nanotubes (BNNTs) via a chemical vapor deposition method, as potential agents for boron neutron capture therapy. BNNTs were functionalized with PAMAM[G-2] dendrimer and then, conjugated with l-Phe using EDC/NHS. After that, BNNTs were radiolabeled with 125/131I, which are commonly used for both therapy and diagnosis in clinical and pre-clinical studies. BNNTs were radiolabeled with a maximum yield with 125/131I in compared with 4-borono-l-phenyalanine which is currently used as a commercial drug. Radiolabeling parameters were optimized with thin layer radiochromatography and high performance liquid radiochromatography. BNNTs are promising nanobioconjugates as new theranostic agents.

Hyaluronic acid-modified [19F]FDG-conjugated magnetite nanoparticles: in vitro bioaffinities and HPLC analyses in organs

In this study, we designed and synthesized [19F]FDG-(2-deoxy-2-[fluorine-19]fluoro-d-glucose) conjugated iron oxide magnetic nanoparticles ([19F]FDG-MNPs) for hybrid imaging and hyperthermia treatment. MNPs were synthesized, silica coated, and fabricated with TEOS (tetraethyl orthosilicate). They were then covered with hyaluronic acid (HA) to enhance their bioavailability. The modified MNPs were conjugated with [19F]FDG and optically labeled with ICG (indocyanine green). The in vitro bioaffinities were surveyed in MCF7 and PC3 cell lines. In vivo bioaffinies were determined using Sprague–Dawley rats.

Radioiodination of cyclin dependent kinase inhibitor Olomoucine loaded Fe@Au nanoparticle and evaluation of the therapeutic efficacy on cancerous cells

Abstract Magnetic nanoparticles have promising biomedical applications such as drug delivery, novel therapeutics and diagnostic imaging. Magnetic drug delivery combination works on the delivery of magnetic nanoparticles loaded with drug to the target tissue by means of an external magnetic field. Gold coated iron oxide (Fe@Au) nanoparticles can provide useful surface chemistry and biological reactivity. Covalent conjugation to the Fe@Au nanoparticles through cleavable linkages can be used to deliver drugs to tumor cells, then the drug can be released by an external. In this paper, purine based cyclin dependent kinases (CDKs) inhibitor Olomoucine (Olo) [2-(Hydroxyethylamino)-6-benzylamino-9-methylpurine] was loaded on gold coated iron oxide (Fe@Au) nanoparticles and radiolabeled with 131I to combine magnetic targeted drug delivery and radiotherapy. Fe@Au nanoparticles were synthesized by microemulsion method. The characterization of nanoparticles was examined by TEM, VSM and XRD. Amine activation was utilized by cysteamine hydrochloride and then CDI was used for conjugation of Olomoucine. Antiproliferative effect and cytotoxicity of Olomoucine loaded Fe@Au nanoparticles (Fe@Au-Olo) were investigated on MCF7 and A549 cell lines. Proliferation rate was decreased while uptake of Fe@Au-Olo on both cell lines was high in comparison with Olomoucine. Also, enhanced incorporation ratio was observed under external magnetic field.

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.

Multifunctional molecular imaging probes for estrogen receptors: 99mTc labeled diethylstilbestrol (DES) conjugated, cuinp quantum dot nanoparticles (DESCIP)

A theranostic nanoparticle was synthesized based on diethylstilbestrol conjugated with phosphate, copper, and indium (DESCIP) and labelled with 99mTc which can be used for SPECT imaging of ER-enriched cancers. In vitro biological activity of 99mTc-DESCIP was examined in breast adenocarcinoma cells (MCF-7), prostatic carcinoma cells (PC-3), and pulmonary epithelial cells (A-549). In vivo lymph node imaging was performed in normal and receptor blocked female New Zealand rabbits. Results demonstrated that 99mTc-DESCIP and DESCIP has potential for imaging ER-enriched tumors such as breast and prostate tumors, and their metastases in the lung, as well as improving management for their therapies.