Mesenchymal stem cells as carriers for systemic delivery of oncolytic viruses

Progress in genetic engineering led to the emergence of some viruses as potent anticancer therapeutics. These oncolytic viruses combine self-amplification with dual antitumor action: oncolytic (destruction of cancer cells) and immunostimulatory (eliciting acquired antitumor response against cancer epitopes). As any other viruses, they trigger antiviral response upon systemic administration. Mesenchymal stem cells are immature cells capable of self-renewing and differentiating into many cell types that belong to three germinal layers. Due to their inherent tumor tropism mesenchymal stem cells loaded with oncolytic virus can improve delivery of the therapeutic cargo to cancer sites. Shielding of oncolytic viral construct from antiviral host immune response makes these cells prospective delivery vehicles to even hard-to-reach metastatic neoplastic foci. Use of mesenchymal stem cells has been criticized by some investigators as limiting proliferative abilities of primary cells and increasing the risk of malignant transformation, as well as attenuating therapeutic responses. However, majority of preclinical studies indicate safety and efficacy of mesenchymal stem cells used as carriers of oncolytic viruses. In view of contradictory postulates, the debate continues. The review discusses mesenchymal stem cells as carriers for delivery of genetically engineered oncolytic constructs and focuses on systemic approach to oncoviral treatment of some deadly neoplasms

Spectroscopic and crystallographic characterization of a new cathinone derivative: 1‑phenyl‑2‑(butylamino)hexan‑1‑one hydrochloride (N‑butylhexedrone)

Purpose In this study, a new cathinone derivative, N-butylhexedrone, emerged on new psychoactive substances (NPS) market in Poland was described and characterized. Methods The compound was analyzed by gas chromatography—mass spectrometry, X-ray crystallography and infrared, Raman, ultraviolet-visible and nuclear magnetic resonance spectroscopic approaches. Results We confirmed the presence of the compound in the seized material and obtained detailed and comprehensive physicochemical characterization of N-butylhexedrone—new cathinone derivative available on the NPS market. Conclusions In this study, we presented chromatographic, spectroscopic and crystallographic characterization of a new cathinone derivative that emerged on the NPS market in 2019. The obtained analytical data should be useful for forensic and toxicological purposes in quick and reliable compound identification

Methotrexate and cytarabine - loaded nanocarriers for multidrug cancer therapy : spectroscopic study

Determining the properties of nanoparticles obtained by novel methods and defining the scope of their application as drug carriers has important practical significance. This article presents the pioneering studies concerning high degree incorporation of cytarabine (AraC) and methotrexate (MTX) into liposome vesicles. The main focus of this study were cytarabine-methotrexate-dipalmitoylphosphatidylcholine (DPPC) interactions observed in the gel and fluid phases of DPPC bilayers. The proposed new method of use the Transmittance2919/2850 ratio presented in our research is sensitive to subtle changes in conformational order resulting from rotations, kinks and bends of the lipid chains. The transition temperatures characterized by Fourier Transform Infrared Spectroscopy (FT-IR) were consistent with the results obtained by Differential Scanning Calorimetry (DSC). Transmission Electron Microscopy (TEM) was used in order to determine the size and shape of the liposomes obtained. The mutual interactions occurring between the drugs studied and the phospholipids were analyzed using the Nuclear Magnetic Resonance (NMR)

Crystal structures and other properties of ephedrone (methcathinone) hydrochloride, N‑acetylephedrine and N‑acetylephedrone

Purpose Three compounds obtained from ephedrine were identified and characterized by various instrumental analytical methods. Ephedrone (methcathinone) hydrochloride and its fundamental derivatives N-acetylephedrine and N-acetylephedrone were analyzed as precursors of a cathinone derivative. Methods The obtained samples were analyzed by gas chromatography coupled with mass spectrometry, nuclear magnetic resonance spectroscopy, infrared and Raman spectroscopy, and X-ray crystallography. Results The three compounds were confirmed as: N-methyl-2-amino-1-phenylpropan-1-one (methcathinone) hydrochloride, N-acetyl-N-methyl-2-amino-1-phenylpropan-1-one (cathinone derivative), and N-acetyl-N-methyl-2-amino-1-phenylpropan- 1-ol (acetyl derivative of ephedrine). Conclusions X-ray crystallography is especially useful for identifying the new designer drugs and their different precursor forms

The synthesis of new potential photosensitizers.[Pt].1 Mono-carboxylic acid derivatives of tetraphenylporphyrin

A series of mono-alkylcarboxylic acid derivatives of tetraphenylporphyrin have been prepared. All the porphyrins were completely characterized by use of mass, 1H NMR, UV–visible, and fluorescence spectroscopy. Experimental log P were determined by use of reversedphase thin-layer chromatography with use of log PRekker. These porphyrins are potential photosensitizers in photodynamic therapy

Spectroscopic characterization and crystal structures of four hydrochloride cathinones : N-ethyl-2-amino-1-phenylhexan-1-one (hexen, NEH), N-methyl-2-amino-1-(4-methylphenyl)-3-methoxypropan-1-one (mexedrone), N-ethyl-2-amino-1-(3,4-methylenedioxyphenyl)pentan-1-one (ephylone) and N-butyl-2-amino-1-(4-chlorophenyl) propan-1-one (4-chlorobutylcathinone)

Purpose Four compounds found during seizure by drug enforcement agencies were identified and characterized by various instrumental analytical methods. Methods The samples were analyzed by nuclear magnetic resonance (NMR), infrared and Raman spectroscopies and X-ray crystallography. Results The four compounds were confirmed as: N-ethyl-2-amino-1-phenylhexan-1-one hydrochloride, N-methyl-2-amino-1-(4-methylphenyl)-3-methoxypropan-1-one hydrochloride, N-ethyl-2-amino-1-(3,4-methylenedioxyphenyl)pentan-1-one hydrochloride and N-butyl-2-amino-1-(4-chlorophenyl)propan-1-one hydrochloride; all four were cathinone derivatives available on the designer drug market. Conclusions X-ray crystallography is especially useful for identifying the new and unknown designer drugs and their enantiomeric forms

Potassium ferrate (VI) as the multifunctional agent in the treatment of landfill leachate

Possible use of potassium ferrate (VI) (K2FeO4) for the treatment of landfill leachate (pH = 8.9, Chemical Oxygen Demand (COD) 770 mg O2/L, Total Organic Carbon (TOC) 230 mg/L, Total Nitrogen (Total N) 120 mg/L, Total Phosphorus (Total P) 12 mg/L, Total Coli Count (TCC) 6.8 log CFU/mL (Colony-Forming Unit/mL), Most Probable Number (MPN) of fecal enterococci 4.0 log/100 mL, Total Proteolytic Count (TPC) 4.4 log CFU/mL) to remove COD was investigated. Central Composite Design (CCD) and Response Surface Methodology (RSM) were applied for modelling and optimizing the purification process. Conformity of experimental and predicted data (R2 = 0.8477, Radj 2 = 0.7462) were verified using Analysis of Variance (ANOVA). Application of K2FeO4 using CCD/RSM allowed to decrease COD, TOC, Total N, Total P, TCC, MPN of fecal enterococci and TPC by 76.2%, 82.6%, 68.3%, 91.6%, 99.0%, 95.8% and 99.3%, respectively, by using K2FeO4 0.390 g/L, at pH = 2.3 within 25 min. Application of equivalent amount of iron (as FeSO4 7H2O and FeCl3 6H2O) under the same conditions allowed to diminish COD, TOC, Total N, Total P, TCC, MPN of fecal enterococci and TPC only by 38.1%, 37.0%, 20.8%, 95.8%, 94.4%, 58.2%, 90.8% and 41.6%, 45.7%, 29.2%, 95.8%, 92.1%, 58.2%, 90.0%, respectively. Thus, K2FeO4 could be applied as an environmentally friendly reagent for landfill leachate treatment

Taguchi method and response surface methodology in the treatment of highly contaminated tannery wastewater using commercial potassium ferrate

The potential implementation of Envifer®, a commercial product containing potassium ferrate (40.1% K2FeO4), for the purification of highly contaminated tannery wastewater from leather dyeing processes was proposed. The employment of the Taguchi method for optimization of experiments allowed the discoloration (98.4%), chemical oxygen demand (77.2%), total organic carbon (75.7%), and suspended solids (96.9%) values to be lowered using 1.200 g/L K2FeO4 at pH 3 within 9 min. The application of the central composite design (CCD) and the response surface methodology (RSM) with the use of 1.400 g/L K2FeO4 at pH 4.5 diminished the discoloration, the chemical oxygen demand, the total organic carbon, and suspended solids within 9 min. The Taguchi method is suitable for the initial implementation, while the RSM is superior for the extended optimization of wastewater treatment processes

Towards property profiling: SYNTHESIS and SAR probing of new tetracyclic diazaphenothiazine analogues

A series of new tertiary phenothiazine derivatives containing a quinoline and a pyridine fragment was synthesized by the reaction of 1-methyl-3-benzoylthio-4-butylthioquinolinium chloride with 3-aminopyridine derivatives bearing various substituents on the pyridine ring. The direction and mechanism of the cyclization reaction of intermediates with the structure of 1-methyl- 4-(3-pyridyl)aminoquinolinium-3-thiolate was related to the substituents in the 2- and 4-pyridine position. The structures of the compounds were analyzed using 1H, 13C NMR (COSY, HSQC, HMBC) and X-ray analysis, respectively. Moreover, the antiproliferative activity against tumor cells (A549, T47D, SNB-19) and a normal cell line (NHDF) was tested. The antibacterial screening of all the compounds was conducted against the reference and quality control strain Staphylococcus aureus ATCC 29213, three clinical isolates of methicillin-resistant S. aureus (MRSA). In silico computation of the intermolecular similarity was performed using principal component analysis (PCA) and hierarchical clustering analysis (HCA) on the pool of structure/property-related descriptors calculated for the novel tetracyclic diazaphenothiazine derivatives. The distance-oriented property evaluation was correlated with the experimental anticancer activities and empirical lipophilicity as well. The quantitative shape-based comparison was conducted using the CoMSA method in order to indicate the potentially valid steric, electronic and lipophilic properties. Finally, the numerical sampling of similarity-related activity landscape (SALI) provided a subtle picture of the SAR trends

Myxoma virus expressing LIGHT (TNFSF14) pre-loaded into adipose-derived mesenchymal stem cells is effective treatment for murine pancreatic adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a weakly immunogenic fatal neoplasm. Oncolytic viruses with dual anti-cancer properties—oncolytic and immune response-boosting effects—have great potential for PDAC management. Adipose-derived stem cells (ADSCs) of mesenchymal origin were infected ex vivo with recombinant myxoma virus (MYXV), which encodes murine LIGHT, also called tumor necrosis factor ligand superfamily member 14 (TNFSF14). The viability and proliferation of ADSCs were not remarkably decreased (1–2 days) following MYXV infection, in sharp contrast to cells of pancreatic carcinoma lines studied, which were rapidly killed by the infection. Comparison of the intraperitoneal (IP) vs. the intravenous (IV) route of ADSC/MYXV administration revealed more pancreas-targeted distribution of the virus when ADSCs were delivered IP to mice bearing orthotopically injected PDAC. The biodistribution, tumor burden reduction and anti-tumor adaptive immune response were examined. Bioluminescence data, used to assess the presence of the luciferase-tagged virus after IP injection, indicated enhanced trafficking into the pancreata of mice bearing orthotopically-induced PDAC, as compared to tumor-free animals, resulting in extended survival of the treated PDAC-seeded animals and in the boosted expression of key adaptive immune response markers. We conclude that ADSCs pre-loaded with transgene-armed MYXV and administered IP allow for the effective ferrying of the oncolytic virus to sites of PDAC and mediate improved tumor regression