Molecular targets for anticancer redox chemotherapy and cisplatin-induced ototoxicity: the role of curcumin on pSTAT3 and Nrf-2 signalling

In oncology, an emerging paradigm emphasises molecularly targeted approaches for cancer prevention and therapy and the use of adjuvant chemotherapeutics to overcome cisplatin limitations. Owing to their safe use, some polyphenols, such as curcumin, modulate important pathways or molecular targets in cancers. This paper focuses on curcumin as an adjuvant molecule to cisplatin by analysing its potential implications on the molecular targets, signal transducer and activator of transcription 3 (STAT3) and NF-E2 p45-related factor 2 (Nrf-2), in tumour progression and cisplatin resistance in vitro and the adverse effect ototoxicity in vivo

Conjugation of glucosamine with Gd3+-based nanoporous silica using a heterobifunctional ANB-NOS crosslinker for imaging of cancer cells

Bita Mehravi,1 Mohsen Ahmadi,1 Massoud Amanlou,2 Ahmad Mostaar,1 Mehdi Shafiee Ardestani,3 Negar Ghalandarlaki4 1Biomedical Engineering and Medical Physics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences,Tehran, Iran; 2Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran, 3Department of RadioPharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, 4Department of Biological Science, School of Science, Science and Research Branch, Islamic Azad University, Tehran, Iran Background: The aim of this study was to synthesize Gd3+-based silica nanoparticles that conjugate easily with glucosamine and to investigate their use as a nanoprobe for detection of human fibrosarcoma cells. Methods: Based on the structure of the 2-fluoro-2-deoxy-D-glucose molecule (18FDG), a new compound consisting of D-glucose (1.1 nm) was conjugated with a Gd3+-based mesoporous silica nanoparticle using an N-5-azido-2-nitrobenzoyloxy succinimide (ANB-NOS) crosslinker. The contrast agent obtained was characterized using a variety of methods, including Fourier transform infrared spectroscopy, nitrogen physisorption, thermogravimetric analysis, scanning and transmission electron microscopy, and inductively coupled plasma atomic emission spectrometry (ICP-AES). In vitro studies included cell toxicity, apoptosis, tumor necrosis factor-alpha, and hexokinase assays, and in vivo tests consisted of evaluation of blood glucose levels using the contrast compound and tumor imaging. The cellular uptake study was validated using ICP-AES. Magnetic resonance relaxivity of the contrast agent was determined using a 1.5 Tesla scanner. Results: ANB-NOS was found to be the preferred linker for attaching glucosamine onto the surface of the mesoporous silica nanospheres. The r1 relaxivity for the nanoparticles was 17.70 mM-1s-1 per Gd3+ ion, which is 4.4 times larger than that for Magnevist® (r1 approximately 4 mM-1s-1 per Gd3+ ion). The compound showed suitable cellular uptake (75.6% ± 2.01%) without any appreciable cytotoxicity. Conclusion: Our results suggest that covalently attaching glucosamine molecules to mesoporous silica nanoparticles enables effective targeted delivery of a contrast agent. Keywords: gadolinium, glucosamine, mesoporous silica nanospheres, magnetic resonance imaging, N-5-azido-2-nitrobenzoyloxy succinimide, photoactivatio

In vitro evaluation of gadolinium-silica mesoporous nanoparticles-monoclonal antibody: Potential nanoprobe for prostate cancer cell imaging

Purpose: The unambiguous prostate cancer diagnosis is of high global interest. Magnetic Resonance Imaging (MRI) is a low invasive modality in early stages of tumor diagnosis, especially for cancer detection. The study aim is to synthesize Gd3+ based silica mesoporous nanosphere conjugated with Monoclonal Antibody (Mab C595) and evaluate its ability as nanoprobe for prostate cancer cells detection. Method: Here, a nanoprobe, specifically recognizing in vivo MUC-1 antigen in prostate cancer cells, was synthesized and evaluated. The in vitro studies included cell toxicity, cell binding and immune reactivity assay. MR imaging parameters of this nanoprobe were investigated by MRI. Results: Results showed that this nanoprobe is a selective MUC-1 detector, without any significant cell toxicity. Conclusion: This study confirmed that this nanoprobe is potentially a selective prostate molecular imaging agent for cancer cell detection. © 2015 Bentham Science Publishers

Cellular uptake and imaging studies of glycosylated silica nanoprobe (GSN) in human colon adenocarcinoma (HT 29 cell line)

Bita Mehravi,1 Mohsen Ahmadi,1 Massoud Amanlou,2 Ahmad Mostaar,1 Mehdi Shafiee Ardestani,3 Negar Ghalandarlaki41Biomedical Engineering and Medical Physics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 4Department of Biological Science, School of Science, Science and Research branch, Islamic Azad University, Tehran, IranPurpose: In recent years, molecular imaging by magnetic resonance imaging (MRI) has gained prominence in the detection of tumor cells. The scope of this study is on molecular imaging and on the cellular uptake study of a glycosylated silica nanoprobe (GSN).Methods: In this study, intracellular uptake (HT 29 cell line) of GSN was analyzed quantitatively and qualitatively with inductively coupled plasma atomic emission spectroscopy, flow cytometry, and fluorescent microscopy. In vitro and in vivo relaxometry of this nanoparticle was determined using a 3 Tesla MRI; biodistribution of GSN and Magnevist® were measured in different tissues.Results: Results suggest that the cellular uptake of GSN was about 70%. The r1 relaxivity of this nanoparticle in the cells was measured to be 12.9 ± 1.6 mM-1 s-1 and on a per lanthanide gadolinium (Gd3+) basis. Results also indicate an average cellular uptake of 0.7 ± 0.009 pg Gd3+ per cell. It should be noted that 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated that the cells were effectively labeled without cytotoxicity, and that using MRI for quantitative estimation of delivery and uptake of targeted contrast agents and early detection of human colon cancer cells using targeted contrast agents, is feasible.Conclusion: These results showed that GSN provided a critical guideline in selecting these nanoparticles as an appropriate contrast agent for nanomedicine applications.Keywords: cellular uptake, contrast agent, glucosamine, mesoporous silica nanospheres, molecular imaging, MR