Multi-stage screening to predict the specific anticancer activity of Ni(II) mixed-ligand complex on gastric cancer cells; biological activity, FTIR spectrum, DNA binding behavior and simulation studies.

The anticancer activity of a transition metal complex with [Ni(L1)2L2]H2O (where L1 and L2 were acetylacetonato (acac) and 2-aminopyridine (2-ampy), respectively) was evaluated in MKN45 cell line. Methyl thiazolyl tetrazolium (MTT) assay was performed to assess the antitumor capacity of the Ni(II) complex against gastric cancer cell line MKN45. The complexexhibited high in vitro antitumor activity against MKN45 cells with IC50values of 1.99 µM in 48 hrs. The alterations in the structure of cellular biomolecules (proteins, lipids, carbohydrates, and especially DNA) by the Ni(II) complex were confirmed by bio spectroscopic studies. Fourier Transformed Infrared (FTIR) spectroscopy analysis revealed significant differences between untreated and treated MKN45 cell line in the region of glycogen, nucleic acid, amide I and amide II bands (1000, 1100, ~1650, and ~1577 cm-1). The absorption bands 1150 cm-1 and 1020-1025 cm-1 can be assigned to the CO bond of glycogen and other carbohydrates and are significantly overlapped by DNA. The interaction of calf thymus (CT) DNA with Ni(II) complex was explored using absorption spectral method. The UV-visible studies demonstrated that this complex was able to bind with DNA via groove, non-covalent, and electrostatic interactions, and binding constant (Kb) was found to be 3 * 104. Docking simulation and Non Covalent Interaction (NCI) topological analysis were conducted to provide insights into the nature of DNA/complex interactions. The binding affinity and binding stability of complex was validated by 400-ns MD simulations.

Optimization of post-insertion method to conjugate Doxil with anti-CD133 monoclonal antibodies: Investigating the specific binding and cytotoxicity to colorectal cancer cells in vitro.

In this paper, Doxil coupled with anti-CD133 monoclonal antibodies made by either routine or optimized post-insertion technique, were compared with respect to their size, drug leakage, release pattern and the number of antibodies conjugated per single liposome. The results demonstrated that the number of antibodies conjugated per liposome in the optimized post-insertion technique was almost two times more than those in the routine post-insertion method. However, the drug release and leakage pattern was almost similar between the two methods. Furthermore, anti-tumor activity and therapeutic efficacy of the preferred CD133-targeted Doxil with Doxil was compared in terms of their in vitro binding, uptake, internalization and cytotoxicity against HT-29 (CD133+) and CHO (CD133-) cells. Flow cytometry analyses and confocal laser scanning microscopy results exhibited a significantly higher cellular uptake, binding and internalization of CD133-targeted Doxil in CD+133 cells relative to Doxil. Cytotoxicity results revealed a lower in vitro inhibitory concentration for CD133-targeted Doxil compared to Doxil. However, CHO (CD133-) cells displayed a similar uptake and in vitro cytotoxicity for both CD133-Doxil and non-targeted Doxil. Therefore, the results of this study can exhibit that specific recognition and binding of antibodies with CD133 receptors on HT-29 cells can result in enhanced cellular uptake, internalization and cytotoxicity. The research suggests further investigation for in vivo studies and may offer proof-of-principle for an active targeting concept.

Effect of Molybdenum Nanoparticles on Blood Cells, Liver Enzymes, and Sexual Hormones in Male Rats.

Despite an increasing surge in application of nanoparticles in industries, there is a serious lack of information concerning their impact on human health and the environment. The present study investigated effects of molybdenum nanoparticles (Mo NPs) injected intraperitoneally into Sprague-Dawley rats at different doses of Mo NPs (5, 10, and 15 mg/kg BW per day) during a period of 28 days. Hematological and biochemical parameters as well as sexual hormones and histopathological examinations of the liver and testis were assessed and compared with control group. The results showed that the serum levels of testosterone decreased significantly in both groups of 10 and 15 mg (Mo NPs)/kg BW in comparison with the control group (p < 0.05). However, there were insignificant differences observed in luteinizing hormone (LH) levels and hematological parameters when compared with the control group (p > 0.05). The results of liver enzymes showed that serum levels of aspartate aminotransferase (AST) decreased significantly in both dosage groups of 5 and 10 mg/kg BW (Mo NPs) when compared with the control group (p < 0.05), and significant decrease obtained in lactate dehydrogenase (LDH) levels at dose of 5 mg/kg BW in comparison with the control group (p < 0.05). The histopathological examination of testis showed a decrease in number of Leydig cells. Also, the number of chronic inflammatory cells increased in portal triad and parenchyma in liver tissue of rats exposed to Mo NPs.