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Targeting mitochondrial metabolism represents a promising approach for cancer treatment. Here, we investigated the mitotoxic potential of the polybrominated diphenyl ether bromoxib, a natural compound isolated from the marine sponge Dysidea family. We could show that bromoxib comprised strong cytotoxicity in different leukemia and lymphoma cell lines (such as HL60, HPBALL, Jurkat, K562, KOPTK1, MOLT4, SUPB15 and Ramos), but also in solid tumor cell lines (such as glioblastoma cell lines SJ-GBM2 and TP365MG). Bromoxib activated the mitochondrial death pathway as evidenced by the rapid translocation of Bax to the mitochondria and the subsequent mitochondrial release of Smac. Accordingly, bromoxib-induced apoptosis was blocked in caspase 9 deficient Jurkat cells and Jurkat cells overexpressing the antiapoptotic protein Bcl-2. In addition, we could show that bromoxib functioned as an uncoupler of the electron transport chain with similar rapid kinetics as CCCP in terms of dissipation of the mitochondrial membrane potential (ΔΨm), processing of the dynamin-like GTPase OPA1 and subsequent fragmentation of mitochondria. Beyond that, bromoxib strongly abrogated ATP production via glycolysis as well as oxidative phosphorylation (OXPHOS) by targeting electron transport chain complexes II, III, and V (ATP-synthase) in Ramos lymphoma cells. Thus, bromoxib's potential to act on both cytosolic glycolysis and mitochondrial respiration renders it a promising agent for the treatment of leukemia and lymphoma. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is characterised by the lack or low expression of estrogen, progesterone, and human epidermal growth factor receptor 2 receptors. TNBC has a high recurrence rate, swiftly metastasizes, and has a high mortality rate. Subsequently, the increase in cases of TNBC has signaled the need for treatment strategies with improved drug delivery systems. New diagnostic approaches, chemical entities, formulations particular those in the nanometric range have emerged after extensive scientific research as alternative strategies for TNBC treatment. As compared to contemporary cancer therapy, nanoparticles offer peculiar tunable features namely small size, shape, electrical charge, magnetic and fluorescent properties. Specifically in targeted drug delivery, nanoparticles have been demonstrated to be highly efficient in encapsulating, functionalization, and conjugation. Presently, nanoparticles have ignited and transformed the approach in photodynamic therapy, bioimaging, use of theranostics and precision medicine delivery in breast cancer. Correspondingly, recent years have witnessed a drastic rise in literature pertaining to treatment of TNBC using nanomaterials. Subsequently, this manuscript aims to present a state-of-the-art of nanomaterials advance on TNBC treatment; the ubiquitous utility use of nanomaterials such as liposomes, dendrimers, solid lipid nanomaterials, gold nanomaterials and quantum dots as anticancer agents and drug delivery systems in TNBC. [ABSTRACT FROM AUTHOR]

Objective(s): Tuberculosis (TB) is one of the most common infectious diseases in the world and requires novel medications or existing ones should be improved. Nanotechnology is a modern science that helps to avoid adverse reactions and resistance to drugs. The current regimen for standard therapy calls for routine administration of medications over six months. Since the noncompliance of patients and the emergence of drug-resistant strains, therapies become more challenging. The objective of the current study was to develop Isoniazid-Rifampicin-loaded (INH-RIF-NPs) nanoparticles to improve release properties and drug encapsulation efficiency. Materials and Methods: Box-Behnken Design (BBD) was used for optimizing the nanoparticles. Eudragit was used in the preparations in varying concentrations (1-2% w/v). The compatibility of the drug and excipients was shown. The existence of the nanoparticles was confirmed by the analytical results of the transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR). Results: The optimized nanoparticles showed no drug-polymer interaction. The mean size of the INH-RIFNPs was around 112±8.73 nm, and they were sphere-like, smooth, fairly uniform in size, and well-dispersed, and entrapment efficiencies were high at 98.7±0.68%. Drug release was slow and sustained with 66.91% INH cumulative release and 80.06 of RFP after 24 hr. Conclusion: Significant drug uptake with higher encapsulation efficiency, uniform size, good dispersion, and prolonged release characteristics are all present in INH-RIF-NPs. This suggests the existence of a delivery system capable of effectively encapsulating and delivery of combined drug formulation in polymeric nanoparticles. [ABSTRACT FROM AUTHOR]

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Aim: To study the active targeting efficacy of phenylboronic acid-modified niclosamide solid lipid nanoparticles (PBA-Niclo-SLN) in triple-negative breast cancer (TNBC). Materials & methods: PBA-Niclo-SLNs were formulated by an emulsification-solvent evaporation method using PBA-associated stearylamine (PBSA) as lipid. The drug uptake and the anticancer propensity of PBA-Niclo-SLN were studied in TNBC (MDA-MB231) cells and tumor-bearing mice. Results: PBA-Niclo-SLN formulation resulted in greater antitumor efficacy by inducing G0/G1 cell cycle arrest and apoptosis. Besides, PBA-Niclo-SLN effectively inhibited STAT3, CD44+/CD24- TNBC stem cell subpopulation, epithelial–mesenchymal transition markers. Besides, PBA-Niclo-SLN selectively accumulated at the tumor site with more significant tumor regression and improved the survivability in TNBC tumor-bearing mice. Conclusion: PBA-Niclo-SLN formulation would be an effective strategy to eradicate TNBC cells (breast cancer stem cells and nonbreast cancer stem cells) efficiently. [ABSTRACT FROM AUTHOR]

Muscarinic acetylcholine receptors have been implicated as potential neuroprotective targets for glaucoma. We tested the hypothesis that the lack of a single muscarinic receptor subtype leads to age-dependent neuron reduction in the retinal ganglion cell layer. Mice with targeted disruption of single muscarinic acetylcholine receptor subtype genes (M1 to M5) and wild-type controls were examined at two age categories, 5 and 15 months, respectively. We found no differences in intraocular pressure between individual mouse groups. Remarkably, in 15-month-old mice devoid of the M1 receptor, neuron number in the retinal ganglion cell layer and axon number in the optic nerve were markedly reduced. Moreover, mRNA expression for the prooxidative enzyme, NOX2, was increased, while mRNA expression for the antioxidative enzymes, SOD1, GPx1 and HO-1, was reduced in aged M1 receptor-deficient mice compared to age-matched wild-type mice. In line with these findings, the reactive oxygen species level was also elevated in the retinal ganglion cell layer of aged M1 receptor-deficient mice. In conclusion, M1 receptor deficiency results in retinal ganglion cell loss in aged mice via involvement of oxidative stress. Based on these findings, activation of M1 receptor signaling may become therapeutically useful to promote retinal ganglion cell survival. [ABSTRACT FROM AUTHOR]