The aim of this study was to prepare a novel targeting drug delivery system for 2-Methoxyestradiol (2ME) in order to improve the clinical application of this antitumor drug. It is based in nanoparticles (NPs) of titanium dioxide (TiO${}_2$) coated with polyethylene glycol (PEG) and loaded with 2ME. A complete IR and Raman characterization have been made to confirm the formation of TiO${}_2$–PEG–2ME composite. Vibrational modes have been assigned for TiO${}_2$, PEG, and 2ME and functionalized TiO${}_2$–PEG and TiO${}_2$–PEG–2ME. The observed variation in peak position of FTIR and Raman of each for these composites has been elucidated in terms of intermolecular interactions between PEG–2ME and TiO${}_2$, obtaining step-by-step the modification processes that were attributed to the conjugation of PEG and 2ME to TiO${}_2$ NPs. Modifying TiO${}_2$ NPs with PEG loaded with the 2ME drug revealed that the titanium dioxide nanocarrier possesses an effective adsorption capability, and we discuss their potential application as a system of drug delivery.

The development of scaffolding obtained by electrospinning is widely used in tissue engineering due to porous and fibrous structures that can mimic the extracellular matrix. In this study, poly (lactic-co-glycolic acid) (PLGA)/collagen fibers were fabricated by electrospinning method and then evaluated in the cell adhesion and viability of human cervical carcinoma HeLa and NIH-3T3 fibroblast for potential application in tissue regeneration. Additionally, collagen release was assessed in NIH-3T3 fibroblasts. The fibrillar morphology of PLGA/collagen fibers was verified by scanning electron microscopy. The fiber diameter decreased in the fibers (PLGA/collagen) up to 0.6 µm. FT-IR spectroscopy and thermal analysis confirmed that both the electrospinning process and the blend with PLGA give structural stability to collagen. Incorporating collagen in the PLGA matrix promotes an increase in the material’s rigidity, showing an increase in the elastic modulus (38%) and tensile strength (70%) compared to pure PLGA. PLGA and PLGA/collagen fibers were found to provide a suitable environment for the adhesion and growth of HeLa and NIH-3T3 cell lines as well as stimulate collagen release. We conclude that these scaffolds could be very effective as biocompatible materials for extracellular matrix regeneration, suggesting their potential applications in tissue bioengineering.

Novel Magnesium Oxide (MgO) nanoparticles (NPs) modified with the polymer polyethylene glycol (PEG) were synthesized as carrier for the anticancer drug 2-Methoxyestradiol (2ME) to improve its clinical application. The functionalized NPs were characterized by Infrared spectroscopy with Fourier transform to elucidate the vibration modes of this conjugate, indicating the formation of the MgO-PEG-2ME nanocomposite. The studies of absorption and liberation determined that MgO-PEG-2ME NPs incorporated 98.51 % of 2ME while liberation of 2ME was constant during 7 days at pH 2, 5 and 7.35. Finally, the MgO-PEG-2ME NPs decreased the viability of the prostate cancer cell line LNCap suggesting that this nanocomposite is suitable as a drug delivery system for anticancer prostate therapy.

Following infection withNeisseria gonorrhoeae, bacteria may ascend into the Fallopian tubes (FT) and induce salpingitis, a major cause of infertility. In the FT, interactions between mucosal epithelial cells and gonococci are pivotal events in the pathogen's infection cycle and the inflammatory response. In the current study, primary FT epithelial cells were infected in vitro with different multiplicities of infection (MOI) of Pil⁺Opa⁺gonococci. Bacteria showed a dose-dependent association with cells and induced the secretion of tumor necrosis factor alpha (TNF-α). A significant finding was that gonococcal infection (MOI = 1) induced apoptosis in approximately 30% of cells, whereas increasing numbers of bacteria (MOI = 10 to 100) did not induce apoptosis. Apoptosis was observed in only 11% of cells with associated bacteria, whereas >84% of cells with no adherent bacteria were apoptotic. TNF-α was a key contributor to apoptosis, since (i) culture supernatants from cells infected with gonococci (MOI = 1) induced apoptosis in naïve cultures, suggesting that a soluble factor was responsible; (ii) gonococcal infection-induced apoptosis was inhibited with anti-TNF-α antibodies; and (iii) the addition of exogenous TNF-α induced apoptosis, which was inhibited by the presence of increasing numbers of bacteria (MOI = 10 to 100). These data suggest that TNF-α-mediated apoptosis of FT epithelial cells is likely a primary host defense mechanism to prevent pathogen colonization. However, epithelial cell-associated gonococci have evolved a mechanism to protect the cells from undergoing TNF-α-mediated apoptosis, and this modulation of the host innate response may contribute to establishment of infection. Understanding the antiapoptotic mechanisms used byNeisseria gonorrhoeaewill inform the pathogenesis of salpingitis and could suggest new intervention strategies for prevention and treatment of the disease.

Estradiol (E₂) is a steroid hormone whose physiological actions are mainly mediated by its interaction with intracellular estrogen receptors (ER) leading to modification on the mRNA and protein synthesis in its target cells. However, estrogens can also activate several intracellular signal transduction cascades by non-genomic mechanisms. Estrogens must be inactivated and removed from blood through its conversion to soluble compounds with an apparent low estrogenic activity and decreased affinity for ER. In this context, 2-methoxyestradiol (2ME₂) is generated by a sequential hydroxylation of E₂ via the enzyme cytochrome P450 isoform 1A1 to produce 2-hydroxyestradiol (2OHE₂) followed by a conjugation reaction catalyzed by the enzyme Catechol-O-Methyltransferase generating 2ME₂ from 2OHE₂. Recent evidence indicates that physiological concentration of 2ME₂ may regulate several biological processes while high concentrations of this metabolite may induce pathophysiological alterations in several tissues. In the last years, 2ME₂ has also been described as a promising anticancer drug although its cellular and molecular mechanisms are still being disclosed. Herein, we will review the available literature concerning the role of 2ME₂ in health and disease. We will focus on to describing the intracellular mechanisms by which 2ME₂ exerts its effects on reproductive and non-reproductive tissues. The promising anticancer effects of 2ME₂ and its synthetic derivatives will also be discussed. Finally, a group of 2ME₂-target genes that could be used as biomarkers of 2ME₂ under physiological or pathophysiological conditions will be reviewed.