scholarly journals Engineered Human Nanoferritin Bearing the Drug Genz-644282 for Cancer Therapy

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 992
Author(s):  
Elisabetta Falvo ◽  
Alessandro Arcovito ◽  
Giamaica Conti ◽  
Giuseppe Cipolla ◽  
Martina Pitea ◽  
...  

Gastrointestinal tumors, including pancreatic and colorectal cancers, represent one of the greatest public health issues worldwide, leading to a million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different types of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors.

Author(s):  
Elisabetta Falvo ◽  
Alessandro Arcovito ◽  
Giamaica Conti ◽  
Giuseppe Cipolla ◽  
Martina Pitea ◽  
...  

Gastrointestinal tumors including pancreatic and colorectal cancers represent one of the greatest public health issues worldwide, leading to million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different type of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors


2020 ◽  
Vol 24 (04) ◽  
pp. 548-562 ◽  
Author(s):  
Semih Gorduk

In this study, the synthesis and characterization of novel 4-chloro-5-((2,3-dihydrobenzo-1,4-benzodioxin-2-yl)methoxy)phthalonitrile (1) and its peripherally octa-substituted Zn(II) (Pc-Zn), In(III) (PcInCI) and Mg(II) (Pc-Mg) phthalocyanine (Pc) derivatives are reported for the first time. FT-IR, elemental analysis, UV-vis, NMR and MS techniques were used for characterization studies of the compounds. Aggregation properties of the compounds were evaluated in DMF, DMSO and THF solvents in different concentrations, and the compounds did not tend to aggregate in these solvents. In addition, photophysicochemical properties such as fluorescence, photodegradation and singlet oxygen quantum yield of the compounds were examined in DMSO, DMF and THF solvents to show the potential use of these novel compounds as photosensitizers for photodynamic therapy (PDT). The effects of zinc, indium and magnesium metals, octa substitutions in peripheral positions and different types of solvents on photophysicochemical properties were investigated. The singlet oxygen quantum yield values of compounds ranged from 0.27 to 0.77 in different solvents. As a result of the photophysicochemical properties, these compounds can be considered as potential candidates for PDT, applications.


Author(s):  
J.B. Posthill ◽  
R.P. Burns ◽  
R.A. Rudder ◽  
Y.H. Lee ◽  
R.J. Markunas ◽  
...  

Because of diamond’s wide band gap, high thermal conductivity, high breakdown voltage and high radiation resistance, there is a growing interest in developing diamond-based devices for several new and demanding electronic applications. In developing this technology, there are several new challenges to be overcome. Much of our effort has been directed at developing a diamond deposition process that will permit controlled, epitaxial growth. Also, because of cost and size considerations, it is mandatory that a non-native substrate be developed for heteroepitaxial nucleation and growth of diamond thin films. To this end, we are currently investigating the use of Ni single crystals on which different types of epitaxial metals are grown by molecular beam epitaxy (MBE) for lattice matching to diamond as well as surface chemistry modification. This contribution reports briefly on our microscopic observations that are integral to these endeavors.


Author(s):  
Soyab A Jamadar ◽  

Cleaning of the AC ducts is the need because it creates problems such as the bad indoor air quality which results in health issues and it also causes the large maintenance of the system. The uncleaned air ducts become home for fungi, dust and harmful microbial. The causes and effects of this thing are mentioned following. The AC ducts can be cleaned through various methodologies i.e. conventional and by using robots. In the conventional system, there is manual cleaning by using some equipment. Cleaning the ducts by using robots would be a good solution for this. Different types of robot systems i.e. crawling robot, articulated robot and inspection robot are deployed for the application. There are different types of robots and their equipment according to size and type of duct. The cleaning of rectangular shape ducts is quite difficult than others. Finally, it results that cleaning ducts is the most important thing and using robots is the best methodology for it.


2020 ◽  
Vol 70 (12) ◽  
pp. 4594-4600

The purpose of this study was to characterize some types of biomass wastes resulted from different activities such as: agriculture, forestry and food industry using thermogravimetric and ICP-MS analyses. Also, it was optimized an ICP-MS method for the determination of As, Cd and Pb from biomass ash samples. The ICP-MS analysis revealed that the highest concentration of metals (As, Cd, Pb) was recorded in the wood waste ash sample, also the thermogravimetric analysis indicated that the highest amount of ash was obtained for the same sample (26.82%). The biomass wastes mentioned in this study are alternative recyclable materials, reusable as pellets and briquettes. Keywords: ash, biomass, ICP-MS, minor elements, TG


2006 ◽  
Vol 50 (4) ◽  
pp. 1228-1237 ◽  
Author(s):  
Nagraj Mani ◽  
Christian H. Gross ◽  
Jonathan D. Parsons ◽  
Brian Hanzelka ◽  
Ute Müh ◽  
...  

ABSTRACT Antibiotics with novel mechanisms of action are becoming increasingly important in the battle against bacterial resistance to all currently used classes of antibiotics. Bacterial DNA gyrase and topoisomerase IV (topoIV) are the familiar targets of fluoroquinolone and coumarin antibiotics. Here we present the characterization of two members of a new class of synthetic bacterial topoII ATPase inhibitors: VRT-125853 and VRT-752586. These aminobenzimidazole compounds were potent inhibitors of both DNA gyrase and topoIV and had excellent antibacterial activities against a wide spectrum of problematic pathogens responsible for both nosocomial and community-acquired infections, including staphylococci, streptococci, enterococci, and mycobacteria. Consistent with the novelty of their structures and mechanisms of action, antibacterial potency was unaffected by commonly encountered resistance phenotypes, including fluoroquinolone resistance. In time-kill assays, VRT-125853 and VRT-752586 were bactericidal against Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, and Haemophilus influenzae, causing 3-log reductions in viable cells within 24 h. Finally, similar to the fluoroquinolones, relatively low frequencies of spontaneous resistance to VRT-125853 and VRT-752586 were found, a property consistent with their in vitro dual-targeting activities.


2021 ◽  
Vol 92 (1) ◽  
Author(s):  
Bruna B. Przybulinski ◽  
Rodrigo G. Garcia ◽  
Maria Fernanda de C. Burbarelli ◽  
Claudia M. Komiyama ◽  
Deivid Kelly Barbosa ◽  
...  
Keyword(s):  

Genetics ◽  
2000 ◽  
Vol 154 (1) ◽  
pp. 437-446 ◽  
Author(s):  
Lisa Girard ◽  
Michael Freeling

Abstract Insertions of Mutator transposons into maize genes can generate suppressible alleles. Mu suppression is when, in the absence of Mu activity, the phenotype of a mutant allele reverts to that of its progenitor. Here we present the characterization of five dominant Mu-suppressible alleles of the knox (knotted1-like homeobox) genes liguleless3 and rough sheath1, which exhibit neomorphic phenotypes in the leaves. RNA blot analysis suggests that Mu suppression affects only the neomorphic aspect of the allele, not the wild-type aspect. Additionally, Mu suppression appears to be exerting its effects at the level of transcription or transcript accumulation. We show that truncated transcripts are produced by three alleles, implying a mechanism for Mu suppression of 5′ untranslated region insertion alleles distinct from that which has been described previously. Additionally, it is found that Mu suppression can be caused by at least three different types of Mutator elements. Evidence presented here suggests that whether an allele is suppressible or not may depend upon the site of insertion. We cite previous work on the knox gene kn1, and discuss our results in the context of interactions between Mu-encoded products and the inherently negative regulation of neomorphic liguleless3 and rough sheath1 transcription.


Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 418
Author(s):  
Paolo Morazzoni ◽  
Paola Vanzani ◽  
Sandro Santinello ◽  
Antonina Gucciardi ◽  
Lucio Zennaro ◽  
...  

A “green” solvent-free industrial process (patent pending) is here described for a grape seed extract (GSE) preparation (Ecovitis™) obtained from selected seeds of Veneto region wineries, in the northeast of Italy, by water and selective tangential flow filtration at different porosity. Since a comprehensive, non-ambiguous characterization of GSE is still a difficult task, we resorted to using an integrated combination of gel permeation chromatography (GPC) and electrospray ionization high resolution mass spectrometry (ESI-HRMS). By calibration of retention time and spectroscopic quantification of catechin as chromophore, we succeeded in quantifying GPC polymers up to traces at n = 30. The MS analysis carried out by the ESI-HRMS method by direct-infusion allows the detection of more than 70 species, at different polymerization and galloylation, up to n = 13. This sensitivity took advantage of the nanoscale shotgun approach, although paying the limit of missed separation of stereoisomers. GPC and MS approaches were remarkably well cross-validated by overlapping results. This simple integrated analytical approach has been used for quality control of the production of Ecovitis™. The emerging feature of Ecovitis™ vs. a popular benchmark in the market, produced by a different technology, is the much lower content of species at low n and the corresponding increase of species at high n.


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