Organosilica colloids as nitric oxide carriers: Pharmacokinetics and biocompatibility.

Nitric oxide (NO) is a potential therapeutic agent for various diseases. However, it is challenging to deliver this unstable, free-radical gaseous molecule in the body. Various nanoparticle-based drug delivery systems have been investigated as promising NO carriers without detailed characterization of their biological fate.

A macrolide from Streptomyces sp. modulates apoptosis and autophagy through Mcl-1 downregulation in human breast cancer cells.

Secondary metabolites in marine organisms exhibit various pharmacological activities against diseases, such as cancer. In this study, the anti-proliferative effect of JBIR-100, a macrolide isolated from Streptomyces sp., was investigated in breast cancer cells.

NDAT Targets PI3K-Mediated PD-L1 Upregulation to Reduce Proliferation in Gefitinib-Resistant Colorectal Cancer.

The property of drug-resistance may attenuate clinical therapy in cancer cells, such as chemoresistance to gefitinib in colon cancer cells. In previous studies, overexpression of PD-L1 causes proliferation and metastasis in cancer cells; therefore, the PD-L1 pathway allows tumor cells to exert an adaptive resistance mechanism in vivo. Nano-diamino-tetrac (NDAT) has been shown to enhance the anti-proliferative effect induced by first-line chemotherapy in various types of cancer, including colorectal cancer (CRC).

Author Correction: FTY720 Induces Autophagy-Associated Apoptosis in Human Oral Squamous Carcinoma Cells, in Part, through a Reactive Oxygen Species/Mcl-1-Dependent Mechanism.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Divaricoside Exerts Antitumor Effects, in Part, by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells.

Cardiac glycosides (CGs), prescribed to treat congestive heart failure and arrhythmias, exert potent antitumor activity. In this study, divaricoside (DIV), a CG isolated from was examined for its antitumor potency in oral squamous cell carcinoma (OSCC) cells. Cell growth was inhibited by DIV in a dose- and time-dependent manner in SCC2095 and OECM-1 OSCC cells using MTT assays.

Formation of organosilica nanoparticles with dual functional groups and simultaneous payload entrapment.

A mixed organosilane system for simultaneous formation of organosilica nanoparticles has been systematically studied for loading of various compounds with a wide range of log P values. The molecule-entrapping system was understood by investigating the effects of adjusting various experimental parameters on particle formation and molecule entrapment. Particularly, rhodamine 6 G (R6G) loaded colloidal particles were prepared and characterised in detail.

A 5' AMP-Activated Protein Kinase Enzyme Activator, Compound 59, Induces Autophagy and Apoptosis in Human Oral Squamous Cell Carcinoma.

5' AMP-activated protein kinase enzyme (AMPK), a master regulator of cellular metabolism, is recognized for its association with various metabolic diseases, inflammation and cancer. In this study, we aimed to investigate the role of compound 59, an AMPK activator, in a panel of oral squamous cell carcinoma (OSCC) cell lines. The antiproliferative effects of compound 59 were assessed by MTT assays, flow cytometry, Western blotting, confocal microscopy and transmission electron microscopy.

S-Nitrosothiols (SNO) as light-responsive molecular activators for post-synthesis fluorescence augmentation in fluorophore-loaded nanospheres.

Dye-loaded, fluorescent nanoparticles (FNPs) have been extensively studied as promising imaging or probing agents for therapeutic and biomedical applications, because of improved photostability and reduced cytotoxicity (compared with free dyes). The synthesis of FNPs often involves entrapment of fluorescent dye molecules into nanostructures, which, however, would encounter a problem associated with the formation of molecular aggregates within the confined matrix space. The formation of nonfluorescent aggregates seems unavoidable for some conventional fluorescent dyes, thereby leading to fluorescent quenching.

FTY720 Induces Autophagy-Associated Apoptosis in Human Oral Squamous Carcinoma Cells, in Part, through a Reactive Oxygen Species/Mcl-1-Dependent Mechanism.

In this study, we interrogated the mechanism by which the immunosuppressant FTY720 mediates anticancer effects in oral squamous cell carcinoma (OSCC) cells. FTY720 differentially suppressed the viability of the OSCC cell lines SCC4, SCC25, and SCC2095 with IC values of 6.1, 6.

Pharmacological exploitation of the phenothiazine antipsychotics to develop novel antitumor agents-A drug repurposing strategy.

Phenothiazines (PTZs) have been used for the antipsychotic drugs for centuries. However, some of these PTZs have been reported to exhibit antitumor effects by targeting various signaling pathways in vitro and in vivo. Thus, this study was aimed at exploiting trifluoperazine, one of PTZs, to develop potent antitumor agents.

A triterpenoid from wild bitter gourd inhibits breast cancer cells.

The antitumor activity of 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al (TCD), a triterpenoid isolated from wild bitter gourd, in breast cancer cells was investigated. TCD suppressed the proliferation of MCF-7 and MDA-MB-231 breast cancer cells with IC50 values at 72 h of 19 and 23 μM, respectively, via a PPARγ-independent manner. TCD induced cell apoptosis accompanied with pleiotrophic biological modulations including down-regulation of Akt-NF-κB signaling, up-regulation of p38 mitogen-activated protein kinase and p53, increased reactive oxygen species generation, inhibition of histone deacetylases protein expression, and cytoprotective autophagy.

Silica Ouzo Effect: Amphiphilic Drugs Facilitate Nanoprecipitation of Polycondensed Mercaptosilanes.

Amphiphilic drugs are therapeutic agents whose molecular structures contain both hydrophobic and hydrophilic portions. Here we report a systematic study on how amphiphilic drugs can assist in silica nanoprecipitation. 3-Mercaptopropyltrimethoxysilane (MPTMS) was used as the sole silica material and 12 amphiphilic drugs spanning a wide spectrum of therapeutic categories were included.

An efficient S-NO-polysilsesquioxane nano-platform for the co-delivery of nitric oxide and an anticancer drug.

Codelivery of nitric oxide (NO) and drugs based on a single nanocarrier is a promising therapeutic strategy. Here, we report a one-step nanoprecipitation method to generate nanoparticles that possess simultaneous NO-donating and doxorubicin releasing properties. S-Nitroso polysilsesquioxane acts like an avid "drug sponge" that attracts drug molecules into nanospheres.

LbL Assembly of Albumin on Nitric Oxide-Releasing Silica Nanoparticles Using Suramin, a Polyanion Drug, as an Interlayer Linker.

Preformed protein corona of nanoparticles can be utilized as a promising formulation strategy for improving nano drug delivery. Nitric oxide (NO) is a labile molecule with extensive therapeutic implications. In this study, we test whether preformation of protein coatings can enhance the performance of NO-delivering nanoparticles.

Nitroxidative chemistry interferes with fluorescent probe chemistry: implications for nitric oxide detection using 2,3-diaminonaphthalene.

Simultaneous production of nitric oxide (NO) and superoxide generates peroxynitrite and causes nitroxidative stress. The fluorometric method for NO detection is based on the formation of a fluorescent product from the reaction of a nonfluorescent probe molecule with NO-derived nitrosating species. Here, we present an example of how nitroxidative chemistry could interact with fluorescent probe chemistry.

Versatile synthesis of thiol- and amine-bifunctionalized silica nanoparticles based on the ouzo effect.

In this article, we report a novel, nanoprecipitation-based method for preparing silica nanoparticles with thiol and amine cofunctionalization. (3-Mercaptopropyl)trimethoxysilane (MPTMS) and 3-aminopropyltrimethoxysilane (APTMS) were used as the organosilane precursors, which were subjected to acid-catalyzed polycondensation in an organic phase containing a water-miscible solvent (e.g.

Direct formation of S-nitroso silica nanoparticles from a single silica source.

Nitric oxide (NO) is a ubiquitous molecule in the body. Because of its multiple pathophysiologic roles, the potential for treating various diseases by the exogenous administration of NO has been under intensive investigation. However, the unstable, radical nature of NO poses a major challenge to the effective delivery of NO.

Cucurbitane Triterpenoid from Momordica charantia Induces Apoptosis and Autophagy in Breast Cancer Cells, in Part, through Peroxisome Proliferator-Activated Receptor γ Activation.

Although the antitumor activity of the crude extract of wild bitter gourd (Momordica charantia L.) has been reported, its bioactive constituents and the underlying mechanism remain undefined. Here, we report that 3 β ,7 β -dihydroxy-25-methoxycucurbita-5,23-diene-19-al (DMC), a cucurbitane-type triterpene isolated from wild bitter gourd, induced apoptotic death in breast cancer cells through peroxisome proliferator-activated receptor (PPAR) γ activation.

Superoxide dismutase as a novel macromolecular nitric oxide carrier: preparation and characterization.

Nitric oxide (NO) is an important molecule that exerts multiple functions in biological systems. Because of the short-lived nature of NO, S-nitrosothiols (RSNOs) are believed to act as stable NO carriers. Recently, sulfhydryl (SH) containing macromolecules have been shown to be promising NO carriers.

Comparative kinetics of thiol oxidation in two distinct free-radical generating systems: SIN-1 versus AAPH.

To study oxidative stress in biological systems, chemical compounds capable of producing free radicals have been widely used. Here, we compared two free-radical generators, 3-morpholinosydnonimine (SIN-1) and 2,2'-azo-bis(2-amidinopropane) hydrochloride (AAPH), by measuring the thiol oxidation kinetics of various thiols. We found that SIN-1 is > 30 times potent in causing thiol oxidation than AAPH.

Role of pirenoxine in the effects of catalin on in vitro ultraviolet-induced lens protein turbidity and selenite-induced cataractogenesis in vivo.

Purpose: In this study, we investigated the biochemical pharmacology of pirenoxine (PRX) and catalin under in vitro selenite/calcium- and ultraviolet (UV)-induced lens protein turbidity challenges. The systemic effects of catalin were determined using a selenite-induced cataractogenesis rat model.

Methods: In vitro cataractogenesis assay systems (including UVB/C photo-oxidation of lens crystallins, calpain-induced proteolysis, and selenite/calcium-induced turbidity of lens crystallin solutions) were used to screen the activity of PRX and catalin eye drop solutions.

Efficient delivery of an antisense oligodeoxyribonucleotide formulated in folate receptor-targeted liposomes.

Background: Folate receptors (FRs) are cellular surface markers for numerous solid tumors and myeloid leukemias. The aim of this study was to develop an antisense oligodeoxyribonucleotide (ODN) carrier targeting FR-overexpressing cancer cells using folate (FA) as the targeting moiety. G3139, a phosphorothioate antisense ODN against human bcl2 mRNA, was evaluated in this study.

Efficient delivery of a Bcl-2-specific antisense oligodeoxyribonucleotide (G3139) via transferrin receptor-targeted liposomes.

A novel transferrin receptor (TfR)-targeted liposomal formulation was synthesized and evaluated for the delivery of a phosphorothioate antisense oligodeoxyribonucleotide (ODN) (G3139, oblimerson sodium, or Genasense) to Bcl-2 in K562 leukemia cells. Liposomes composed of DC-Chol/egg PC/PEG-DSPE (25:73.5:1.

Tumor-targeted gene delivery via anti-HER2 antibody (trastuzumab, Herceptin) conjugated polyethylenimine.

A series of novel nonviral vectors targeting the HER-2/neu gene product human epidermal growth factor receptor-2 (HER2) were constructed and evaluated in breast cancer cell lines to optimize vector formulation for receptor-specific gene transfer. These vectors were DNA/polycation complexes (polyplexes) prepared by mixing, at varying ratios, plasmid DNA carrying a luciferase reporter gene to HerPEI, which is a conjugate of linear polyethylenimine (PEI), a cationic polymer, and trastuzumab (Herceptin), a HER2-specific monoclonal antibody. Transfection studies were carried out in both HER2 overexpressing Sk-Br-3 and HER2 low-expressing MDA-MB-231 breast cancer cells.