Impact of Rhenium(I)-Diselenoether Compound on Cell Adhesion, Migration, Invasion Capacities, and MMP-2 Release in MDA-MB-231 Breast Cancer Cells.

Background/aim: Organometallic complexes can decrease adhesion, migration, invasion of cancer cells, mainly through regulation of the extracellular matrix and therefore act against metastases. The aim was to investigate the anti-invasive properties of a rhenium-based metal compound, rhenium(I)-diselenoether (Re-diSe) and its effects on matrix metalloproteinase MMP-2, a key player in metastatic processes, in cultured MDA-MB231 triple-negative breast cancer cells.

Materials And Methods: Matrigel was utilized to assess cancer cell adhesion to the extracellular matrix.

Raman imaging for monitoring deuterated squalene-gemcitabine nanomedicines in single living breast cancer cells.

We have investigated the impact of gemcitabine (Gem) and deuterated gemcitabine-squalene (GemSQ-d6) nanoparticles (NPs) on MCF7 and MDA-MB-231 breast cancer cell lines by Raman spectroscopy. Quantification of LDL expression levels in both cell lines revealed a four-fold increase in MDA-MB-231 cells compared to MCF7 cells. In in vitro antitumor assessments, Gem displayed 13.

A small-molecule hemostatic agent for the reversal of direct oral anticoagulant-induced bleeding.

Background: The bleeding risk associated with direct oral anticoagulants (DOACs) remains a major concern, and rapid reversal of anticoagulant activity may be required. Although specific and nonspecific hemostatic biotherapies are available, there is a need for small-molecule DOAC reversal agents that are simple and cost-effective to produce, store, and administer.

Objectives: To identify and characterize a small molecule with procoagulant activity as a DOAC reversal agent.

Effectiveness of Rhenium(I)-diselenoether Low Doses in a Triple-negative Breast Cancer Chicken Embryo Model.

Background/aim: Rhenium(I)-diselenoether (Re-diSe) is a promising anticancer agent composed of one rhenium and two selenium atoms. Its effectiveness was established in inhibiting cancer cells while maintaining low toxicity toward normal cells at a 5 μM dose for 120 hours in MDA-MB-231 cells. In MDA-MB-231 breast tumor-bearing mice, anti-tumor and anti-metastatic effects were observed at a 10 mg/kg dose.

Remarkable Effects of a Rhenium(I)-diselenoether Drug on the Production of Cathepsins B and S by Macrophages and their Polarizations.

Background/objective: Tumor-associated macrophages (TAMs) produce an excessive amount of cysteine proteases, and we aimed to study the effects of anticancer rhenium(I)-diselenoether (Re-diSe) on the production of cathepsins B and S by macrophages. We investigated the effect of Re-diSe on lipopolysaccharides (LPS) induced M1 macrophages, or by interleukin 6 (IL-6) induced M2 macrophages.

Methods: Non-stimulated or prestimulated murine Raw 264 or human THP-1 macrophages were exposed to increasing concentrations of the drug (5, 10, 20, 50 and 100 μM) and viability was assayed by the MTT assay.

Development and Characterization of Innovative Multidrug Nanoformulation for Cardiac Therapy.

For several decades, various peptides have been under investigation to prevent ischemia/reperfusion (I/R) injury, including cyclosporin A (CsA) and Elamipretide. Therapeutic peptides are currently gaining momentum as they have many advantages over small molecules, such as better selectivity and lower toxicity. However, their rapid degradation in the bloodstream is a major drawback that limits their clinical use, due to their low concentration at the site of action.

Degradation of Polymer-Drug Conjugate Nanoparticles Based on Lactic and Itaconic Acid.

Tuberculosis (TB) is still a significant threat to human health. A promising solution is engineering nanoparticulate drug carriers to deliver anti-TB molecules. Itaconic acid (ITA) potentially has anti-TB activity; however, its incorporation in nanoparticles (NP) is challenging.

Quantification of drug loading in polymeric nanoparticles using AFM-IR technique: a novel method to map and evaluate drug distribution in drug nanocarriers.

Researchers are increasingly thinking smaller to solve some of the biggest challenges in nanomedicine: the control of drug encapsulation. Although recent years have witnessed a significant increase in the development and characterization of polymeric drug nanocarriers, several key features are still to be addressed: Where is the drug located within each nanoparticle (NP)? How much drug does each NP contain? Is the drug loading homogeneous on an individual NP basis? To answer these questions, individual NP characterization was achieved here by using atomic force microscopy-infrared spectroscopy (AFM-IR). A label-free quantification methodology was proposed to estimate with a nanoscale resolution the drug loadings of individual poly(lactic acid) (PLA) NPs loaded with an anticancer drug.

Mannosylation of budesonide palmitate nanoprodrugs for improved macrophage targeting.

In a strategy to improve macrophage targeting of glucocorticoids (GCs) for anti-inflammatory therapy, a so-called nanoprodrug of budesonide palmitate decorated by mannose moieties was designed. The synthesis of budesonide palmitate (BP) was obtained by esterification and mannosylated lipid (DSPE-PEG-Man) by reacting 1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine (DSPE)-polyethylene glycol-amine and α-D-mannopyranosylphenyl isothiocyanate (MPITC). Nanoparticles were formulated by emulsion-evaporation and different ratios of mannosylated lipid were introduced in the formulation of BP nanoprodrugs.

The NSP14/NSP10 RNA repair complex as a Pan-coronavirus therapeutic target.

The risk of zoonotic coronavirus spillover into the human population, as highlighted by the SARS-CoV-2 pandemic, demands the development of pan-coronavirus antivirals. The efficacy of existing antiviral ribonucleoside/ribonucleotide analogs, such as remdesivir, is decreased by the viral proofreading exonuclease NSP14-NSP10 complex. Here, using a novel assay and in silico modeling and screening, we identified NSP14-NSP10 inhibitors that increase remdesivir's potency.

Effects of Rhenium(I)-diselenoether and of its Diselenide Ligand on the Production of Cathepsins B and S by MDA-MB231 Breast Malignant Cells.

Background/aim: Rhenium(I)-diselenoether (Re-diSe) is a drug under development for the treatment of metastatic cancers, with selective inhibitory effects on MDA-MB231 cancer cells compared to normal HEK-293 cells, and with greater effects than its diselenide (di-Se) ligand. Rhenium (Re) compounds inhibit cathepsins, which are important proteolytic enzymes in cancer. This study investigated the effects of Re-diSe and di-Se on the production of cathepsins B and S in MDA-MB231 malignant and HEK-293 normal cells and their inhibitory effects following treatment with different doses for 72 h.

Decoration of Squalenoyl-Gemcitabine Nanoparticles with Squalenyl-Hydroxybisphosphonate for the Treatment of Bone Tumors.

Therapeutic perspectives of bone tumors such as osteosarcoma remain restricted due to the inefficacy of current treatments. We propose here the construction of a novel anticancer squalene-based nanomedicine with bone affinity and retention capacity. A squalenyl-hydroxybisphosphonate molecule was synthetized by chemical conjugation of a 1-hydroxyl-1,1-bisphosphonate moiety to the squalene chain.

Gemcitabine lipid prodrug nanoparticles: Switching the lipid moiety and changing the fate in the bloodstream.

A simple approach to achieve a lipoprotein (LP)-mediated drug delivery is to trigger the spontaneous drug insertion into endogenous lipoproteins in the bloodstream, by means of its chemical modification. Nanoparticles (NPs) made of the squalene-gemcitabine (SQGem) conjugate were found to have a high affinity for plasma lipoproteins while free gemcitabine did not, suggesting a key role of the lipid moiety in this event. Whether the drug conjugation to cholesterol, one of the major lipoprotein-transported lipids, could also promote an analogous interaction was a matter of question.

Investigation of squalene-doxorubicin distribution and interactions within single cancer cell using Raman microspectroscopy.

Intracellular distribution of doxorubicin (DOX) and its squalenoylated (SQ-DOX) nanoparticles (NPs) form in murine lung carcinoma M109 and human breast carcinoma MDA-MB-231 cells was investigated by Raman microspectroscopy. Pharmacological data showed that DOX induced higher cytotoxic effect than SQ-DOX NPs. Raman data were obtained using single-point measurements and imaging on the whole cell areas.

Gemcitabine Lipid Prodrugs: The Key Role of the Lipid Moiety on the Self-Assembly into Nanoparticles.

A small library of amphiphilic prodrugs has been synthesized by conjugation of gemcitabine (Gem) (a hydrophilic nucleoside analogue) to a series of lipid moieties and investigated for their capacity to spontaneously self-assemble into nanosized objects by simple nanoprecipitation. Four of these conjugates formed stable nanoparticles (NPs), while with the others, immediate aggregation occurred, whatever the tested experimental conditions. Whether such capacity could have been predicted based on the prodrug physicochemical features was a matter of question.

Squalenoyl siRNA PMP22 nanoparticles are effective in treating mouse models of Charcot-Marie-Tooth disease type 1 A.

Charcot-Marie-Tooth disease type 1 A (CMT1A) lacks an effective treatment. We provide a therapy for CMT1A, based on siRNA conjugated to squalene nanoparticles (siRNA PMP22-SQ NPs). Their administration resulted in normalization of Pmp22 protein levels, restored locomotor activity and electrophysiological parameters in two transgenic CMT1A mouse models with different severity of the disease.

New Nanoparticle Formulation for Cyclosporin A: In Vitro Assessment.

Cyclosporin A (CsA) is a molecule with well-known immunosuppressive properties. As it also acts on the opening of mitochondrial permeability transition pore (mPTP), CsA has been evaluated for ischemic heart diseases (IHD). However, its distribution throughout the body and its physicochemical characteristics strongly limit the use of CsA for intravenous administration.

Synthesis and Biopharmaceutical Characterization of Amphiphilic Squalenyl Derivative Based Versatile Drug Delivery Platform.

Limited drug loading capacity (LC), mostly below 5% w/w, is a significant drawback of nanoparticulate drug delivery systems (DDS). Squalenoylation technology, which employs bioconjugation of squalenyl moiety and drug, allows self-assemble of nanoparticles (NPs) in aqueous media with significantly high LC (>30% w/w). The synthesis and particle preparation of squalenoylated prodrugs are, however, not facile for molecules with multiple reactive groups.

Combinatorial Nanomedicine Made of Squalenoyl-Gemcitabine and Edelfosine for the Treatment of Osteosarcoma.

Due to chemoresistance and a high propensity to form lung metastasis, survival rates in pediatric osteosarcoma (OS) are poor. With the aim to improve anticancer activity in pediatric OS, a multidrug nanomedicine was designed using the alkyl-lysophospholipid edelfosine (EF) co-assembled with squalenoyl-gemcitabine (SQ-Gem) to form nanoassemblies (NAs) of 50 nm. SQ-Gem/EF NAs modified the total Gem pool exposure in the blood stream in comparison with SQ-Gem NAs, which correlated with a better tolerability and a lower toxicity profile after multiple intravenous administrations in mice.

Inhibition of Ebola infection by anti-parasitic quinoline derivatives.

There continues to be no approved drugs for the treatment of Ebola virus disease (EVD). Despite a number of candidate drugs showing limited efficacy and/or in non-human primate studies, EVD continues to plaque certain areas of Africa without any efficacious treatments yet available. Recently, we have been exploring the potential for anti-malarial drugs to inhibit an model of Ebola Zaire replication using a transcription-competent virus-like particle (trVLP) assay.

Squalenyl Hydrogen Sulfate Nanoparticles for Simultaneous Delivery of Tobramycin and an Alkylquinolone Quorum Sensing Inhibitor Enable the Eradication of P. aeruginosa Biofilm Infections.

Elimination of pulmonary Pseudomonas aeruginosa (PA) infections is challenging to accomplish with antibiotic therapies, mainly due to resistance mechanisms. Quorum sensing inhibitors (QSIs) interfering with biofilm formation can thus complement antibiotics. For simultaneous and improved delivery of both active agents to the infection sites, self-assembling nanoparticles of a newly synthesized squalenyl hydrogen sulfate (SqNPs) were prepared.

A New Model Applied for Evaluating a Rhenium-diselenium Drug: Breast Cancer Cells Stimulated by Cytokines Induced from Polynuclear Cells by LPS.

Background/aim: New anticancer drugs are usually tested on cancer cells in culture in a standard medium. We stimulated immune polynuclear cells by lipopolysaccharides to obtain an enriched medium (EM) containing inflammatory cytokines more closely reflecting the tumor microenvironment and tested a rhenium-diselenium (Re-diSe) drug in this new model. Concentrations of cytokines were compared with a control medium (CM).

A Self-Assembling NHC-Pd-Loaded Calixarene as a Potent Catalyst for the Suzuki-Miyaura Cross-Coupling Reaction in Water.

Nanoformulated calix[8]arenes functionalized with -heterocyclic carbene (NHC)-palladium complexes were found to be efficient nano-reactors for Suzuki-Miyaura cross-coupling reactions of water soluble iodo- and bromoaryl compounds with cyclic triol arylborates at low temperature in water without any organic co-solvent. Combined with an improved one-step synthesis of triol arylborates from boronic acid, this remarkably efficient new tool provided a variety of 4'-arylated phenylalanines and tyrosines in good yields at low catalyst loading with a wide functional group tolerance.

Albumin-driven disassembly of lipidic nanoparticles: the specific case of the squalene-adenosine nanodrug.

In the field of nanomedicine, nanostructured nanoparticles (NPs) made of self-assembling prodrugs emerged in the recent years with promising properties. In particular, squalene-based drug nanoparticles have already shown their efficiency through in vivo experiments. However, a complete pattern of their stability and interactions in the blood stream is still lacking.