Naturally derived DNA nanogels as pH- and glutathione-triggered anticancer drug carriers.

Conventional chemotherapeutic drugs are nonselective and harmful toward normal tissues, causing severe side effects. Therefore, the development of chemotherapeutics that can target cancer cells and improve therapeutic efficacy is of high priority. Biomolecules isolated from nature serve as green solutions for biomedical use, solving biocompatibility and cytotoxicity issues in human bodies. Herein, we use kiwifruit-derived DNA to encapsulate doxorubicin (DOX) using crosslinkers, eventually forming DNA-DOX nanogels (NGs). Drug releasing assays, cell viability and anticancer effects were analyzed to evaluate the DNA NGs' applications. The amount of DOX released by the DOX-loaded DNA (DNA-DOX) NGs at acidic pH was higher than that of neutral pH, and high glutathione (GSH) concentration also triggered more DOX to release in cancer cells, demonstrating pH- and GSH-triggered drug release characteristics of the DNA NGs. The IC50 of DNA-DOX NGs in cancer cells was lower than that of free DOX. Moreover, DOX uptake of cancer cells and apoptotic death were enhanced by the DNA-DOX NGs compared to free DOX. The results suggest that the DNA NGs cross-linked via nitrogen bases of the nucleotides in DNA and presenting pH- and GSH-dependent drug releasing behavior can be alternative biocompatible drug delivery systems for anticancer strategies and other biomedical applications.

Peptide Fibrillar Assemblies Exhibit Membranolytic Effects and Antimetastatic Activity on Lung Cancer Cells.

Cancer metastasis is a central oncology concern that worsens patient conditions and increases mortality in a short period of time. During metastatic events, mitochondria undergo specific physiological alterations that have emerged as notable therapeutic targets to counter cancer progression. In this study, we use drug-free, cationic peptide fibrillar assemblies (PFAs) formed by poly(L-Lysine)-block-poly(L-Threonine) (Lys-b-Thr) to target mitochondria. These PFAs interact with cellular and mitochondrial membranes via electrostatic interactions, resulting in membranolysis. Charge repulsion and hydrogen-bonding interactions exerted by Lys and Thr segments dictate the packing of the peptides and enable the PFAs to display enhanced membranolytic activity toward cancer cells. Cytochrome c (cyt c), endonuclease G, and apoptosis-inducing factor were released from mitochondria after treatment of lung cancer cells, subsequently inducing caspase-dependent and caspase-independent apoptotic pathways. A metastatic xenograft mouse model was used to show how the PFAs significantly suppressed lung metastasis and inhibited tumor growth, while avoiding significant body weight loss and mortality. Antimetastatic activities of PFAs are also demonstrated by in vitro inhibition of lung cancer cell migration and clonogenesis. Our results imply that the cationic PFAs achieved the intended and targeted mitochondrial damage, providing an efficient antimetastatic therapy.

The Inhibitory Mechanism of Gentamicin on Electrical Field Stimulation Response in Rat Bladder Smooth Muscle

To see the inhibitory mechanism of gentamicin in response to electrical field stimulation (EFS) using the rat bladder smooth muscle, atropine or guanethidine was treated but had no effect. Methylsergide, a non-selective 5-HT1, 5-HT2 receptor antagonist was also treated but had on effect. Kinase inhibitors, such as chelerythrine (PKC inhibitor), ML-9 (MLCK inhibitor), or Y27632 (rho kinase inhibitor) were pretreated before gentamicin treatment, but did not have effect. For U73122, a phospholipase C (PLC) inhibitor however, the inhibitory effect to gentamicin was significantly attenuated in all frequencies given by the EFS. Therefore gentamicin induced inhibitory effect on EFS response in rat bladder smooth muscle was not mediated by the activation of adrenergic, cholinergic, or serotonergic receptor. The inhibition of gentamicin might be mediated through the PLC dependent pathway, but not through the PKC, MLCK or rho kinase dependent pathway.

Effect of ECQ on Iodoacetamide-Induced Chronic Gastritis in Rats

This study investigated effect of extract containing quercetin-3-O-beta-D-glucuronopyranoside from Rumex Aquaticus Herba (ECQ) against chronic gastritis in rats. To produce chronic gastritis, the animals received a daily intra-gastric administration of 0.1 ml of 0.15% iodoacetamide (IA) solution for 7 days. Daily exposure of the gastric mucosa to IA induced both gastric lesions and significant reductions of body weight and food and water intake. These reductions recovered with treatment with ECQ for 7 days. ECQ significantly inhibited the elevation of the malondialdehyde levels and myeloperoxidase activity, which were used as indices of lipid peroxidation and neutrophil infiltration. ECQ recovered the level of glutathione, activity of superoxide dismutase (SOD), and expression of SOD-2. The increased levels of total NO concentration and iNOS expression in the IA-induced chronic gastritis were significantly reduced by treatment with ECQ. These results suggest that the ECQ has a therapeutic effect on chronic gastritis in rats by inhibitory actions on neutrophil infiltration, lipid peroxidation and various steps of reactive oxygen species (ROS) generation.