In vitro biological evaluation of a novel folic acid-targeted receptor quantum dot-ß-cyclodextrin carrier for C-2028 unsymmetrical bisacridine in the treatment of human lung and prostate cancers.

BACKGROUND: Traditional small-molecule chemotherapeutics usually do not distinguish tumors from healthy tissues. However, nanotechnology creates nanocarriers that selectively deliver drugs to their site of action. This work is the next step in the development of the quantum dot-ß-cyclodextrin-folic acid (QD-ß-CD-FA) platform for targeted and selected delivery of C-2028 unsymmetrical bisacridine in cancer therapy. METHODS: Herein, we report an initial biological evaluation (using flow cytometry and light microscopy) as well as cell migration analysis of QD-ß-CD(C-2028)-FA nanoconjugate and its components in the selected human lung and prostate cancer cells, as well as against their respective normal cells. RESULTS: C-2028 compound induced apoptosis, which was much stronger in cancer cells compared to normal cells. Conjugation of C-2028 with QDgreen increased cellular senescence, while the introduction of FA to the conjugate significantly decreased this process. C-2028 nanoencapsulation also reduced cell migration. Importantly, QDgreen and QDgreen-ß-CD-FA themselves did not induce any toxic responses in studied cells. CONCLUSIONS: In conclusion, the results demonstrate the high potential of a novel folic acid-targeted receptor quantum dot-ß-cyclodextrin carrier (QDgreen-ß-CD-FA) for drug delivery in cancer treatment. Nanoplatforms increased the amount of delivered compounds and demonstrated high suitability.

Ag-In-Zn-S alloyed nanocrystals as photocatalysts of controlled light-mediated radical polymerization.

We report on the first case of the use of nonstoichiometric ternary (Ag-In-Zn-S) semiconductor nanocrystals as photoinitiators and photocatalysts of methyl methacrylate (MMA) polymerization. Two types of nanocrystals were tested, differing in their composition and characterized by red (λmax = 731 nm) and green (λmax = 528 nm) photoluminescence, respectively. Exploiting their reducing properties and capability of free radical generation we demonstrate that under ultraviolet (UV) radiation they effectively photoinitiate radical polymerization of MMA whereas under visible light (blue or green) they act as photocatalysts of living radical polymerization.

Novel Additives in Copper Electrorefining-Small Laboratory Scale.

This research aimed to evaluate the effectiveness of new organic substances, including a novel ionic liquid based on polyhexamethylenebiguanidine, polyhexamethyleneguanidine, and safranin in the copper electrorefining process. Experiments were conducted on a small laboratory scale using industrial copper anodes. Single doses of new additives did not improve process indicators (current efficiency, average cell voltage, specific energy consumption) or the quality of copper cathode deposits. However, a combination of a new ionic liquid based on polyhexamethylenebiguanidine and thiourea resulted in a satisfactory current efficiency of 97%, an average cell voltage of 0.110 V, a low specific energy consumption index of approximately 100 kWh/tCu, and smooth cathode surfaces. These results were superior to those obtained with industrial additives (bone glue and thiourea). The findings enhance our understanding of how these substances influence the electrorefining process and suggest the potential for more efficient and sustainable methods. Further research is recommended to validate these findings and explore their industrial applications.

pH-Responsive Drug Delivery Nanoplatforms as Smart Carriers of Unsymmetrical Bisacridines for Targeted Cancer Therapy.

Selective therapy and controlled drug release at an intracellular level remain key challenges for effective cancer treatment. Here, we employed folic acid (FA) as a self-navigating molecule in nanoconjugates containing quantum dots (QDs) and ß-cyclodextrin (ß-CD) for the delivery of antitumor unsymmetrical bisacridine compound (C-2028) to lung and prostate cancers as well as normal cells. The bisacridine derivative can form the inclusion complex with ß-cyclodextrin molecule, due to the presence of a planar fragment in its structure. The stability of such a complex is pH-dependent. The drug release profile at different pH values and the mechanism of C-2028 release from QDs-ß-CD-FA nanoconjugates were investigated. Next, the intracellular fate of compounds and their influence on lysosomal content in the cells were also studied. Confocal Laser Scanning Microscopy studies proved that all investigated compounds were delivered to acidic organelles, the pH of which promoted an increased release of C-2028 from its nanoconjugates. Since the pH in normal cells is higher than in cancer cells, the release of C-2028 from its nanoconjugates is decreased in these cells. Additionally, we obtained the concentration profiles of C-2028 in the selected cells treated with unbound C-2028 or nanoconjugate by the HPLC analysis.

Emulsion Explosives: A Tutorial Review and Highlight of Recent Progress.

Emulsion explosives (EE) have been commercially available in various forms for over 50 years. Over this period, the popularity and production technology of this class of energetic materials have been developing constantly. Despite this rapid rise to prominence and, in some applications, prevalence over traditional energetic materials, remarkably little information is available on the physicochemical and energetic properties of these materials and factors affecting those properties. This work is dedicated to presenting the fundamental information relevant to the features, properties and applications of EEs, while highlighting the most significant recent progress pertaining to those materials. Particular emphasis has been given to providing information about the types, composition, modifications and detonation parameters of EEs, as well as to highlighting the less obvious, emerging applications of EEs.

Foliate-Targeting Quantum Dots-ß-Cyclodextrin Nanocarrier for Efficient Delivery of Unsymmetrical Bisacridines to Lung and Prostate Cancer Cells.

Targeted drug delivery by nanocarriers molecules can increase the efficiency of cancer treatment. One of the targeting ligands is folic acid (FA), which has a high affinity for the folic acid receptors, which are overexpressed in many cancers. Herein, we describe the preparation of the nanoconjugates containing quantum dots (QDs) and ß-cyclodextrin (ß-CD) with foliate-targeting properties for the delivery of anticancer compound C-2028. C-2028 was bound to the nanoconjugate via an inclusion complex with ß-CD. The effect of using FA in QDs-ß-CD(C-2028)-FA nanoconjugates on cytotoxicity, cellular uptake, and the mechanism of internalization in cancer (H460, Du-145, and LNCaP) and normal (MRC-5 and PNT1A) cells was investigated. The QDs-ß-CD(C-2028)-FA were characterized using DLS (dynamic light scattering), ZP (zeta potential), quartz crystal microbalance with dissipation (QCM-D), and UV-vis spectroscopy. The conjugation of C-2028 with non-toxic QDs or QDs-ß-CD-FA did not change the cytotoxicity of this compound. Confocal microscopy studies proved that the use of FA in nanoconjugates significantly increased the amount of delivered compound, especially to cancer cells. QDgreen-ß-CD(C-2028)-FA enters the cells through multiple endocytosis pathways in different levels, depending on the cell line. To conclude, the use of FA is a good self-navigating molecule in the QDs platform for drug delivery to cancer cells.

Indium(II) Chloride as a Precursor in the Synthesis of Ternary (Ag-In-S) and Quaternary (Ag-In-Zn-S) Nanocrystals.

A new indium precursor, namely, indium(II) chloride, was tested as a precursor in the synthesis of ternary Ag-In-S and quaternary Ag-In-Zn-S nanocrystals. This new precursor, being in fact a dimer of Cl2In-InCl2 chemical structure, is significantly more reactive than InCl3, typically used in the preparation of these types of nanocrystals. This was evidenced by carrying out comparative syntheses under the same reaction conditions using these two indium precursors in combination with the same silver (AgNO3) and zinc (zinc stearate) precursors. In particular, the use of indium(II) chloride in combination with low concentrations of the zinc precursor yielded spherical-shaped (D = 3.7-6.2 nm) Ag-In-Zn-S nanocrystals, whereas for higher concentrations of this precursor, rodlike nanoparticles (L = 9-10 nm) were obtained. In all cases, the resulting nanocrystals were enriched in indium (In/Ag = 1.5-10.3). Enhanced indium precursor conversion and formation of anisotropic, longitudinal nanoparticles were closely related to the presence of thiocarboxylic acid type of ligands in the reaction mixture. These ligands were generated in situ and subsequently bound to surfacial In(III) cations in the growing nanocrystals. The use of the new precursor of enhanced reactivity facilitated precise tuning of the photoluminescence color of the resulting nanocrystals in the spectral range from ca. 730 to 530 nm with photoluminescence quantum yield (PLQY) varying from 20 to 40%. The fabricated Ag-In-S and Ag-In-Zn-S nanocrystals exhibited the longest, reported to date, photoluminescence lifetimes of ∼9.4 and ∼1.4 µs, respectively. It was also demonstrated for the first time that ternary (Ag-In-S) and quaternary (Ag-In-Zn-S) nanocrystals could be applied as efficient photocatalysts, active under visible light (green) illumination, in the reaction of aldehydes reduction to alcohols.

Organic-to-Aqueous Phase Transfer of Alloyed AgInS2-ZnS Nanocrystals Using Simple Hydrophilic Ligands: Comparison of 11-Mercaptoundecanoic Acid, Dihydrolipoic Acid and Cysteine.

The exchange of primary hydrophobic ligands for hydrophilic ones was studied for two types of alloyed AgInS2-ZnS nanocrystals differing in composition and by consequence exhibiting two different emission colors: red (R) and green (G). Three simple hydrophilic ligands were tested, namely, 11-mercaptoundecanoic acid, dihydrolipoic acid and cysteine. In all cases, stable aqueous colloidal dispersions were obtained. Detailed characterization of the nanocrystal surface before and after the ligand exchange by NMR spectroscopy unequivocally showed that the exchange process was the most efficient in the case of dihydrolipoic acid, leading to the complete removal of the primary ligands with a relatively small photoluminescence quantum yield drop from 68% to 40% for nanocrystals of the R type and from 48% to 28% for the G ones.

Quantum Dots as a Good Carriers of Unsymmetrical Bisacridines for Modulating Cellular Uptake and the Biological Response in Lung and Colon Cancer Cells.

Nanotechnology-based drug delivery provides a promising area for improving the efficacy of cancer treatments. Therefore, we investigate the potential of using quantum dots (QDs) as drug carriers for antitumor unsymmetrical bisacridine derivatives (UAs) to cancer cells. We examine the influence of QD-UA hybrids on the cellular uptake, internalization (Confocal Laser Scanning Microscope), and the biological response (flow cytometry and light microscopy) in lung H460 and colon HCT116 cancer cells. We show the time-dependent cellular uptake of QD-UA hybrids, which were more efficiently retained inside the cells compared to UAs alone, especially in H460 cells, which could be due to multiple endocytosis pathways. In contrast, in HCT116 cells, the hybrids were taken up only by one endocytosis mechanism. Both UAs and their hybrids induced apoptosis in H460 and HCT116 cells (to a greater extent in H460). Cells which did not die underwent senescence more efficiently following QDs-UAs treatment, compared to UAs alone. Cellular senescence was not observed in HCT116 cells following treatment with both UAs and their hybrids. Importantly, QDgreen/red themselves did not provoke toxic responses in cancer or normal cells. In conclusion, QDs are good candidates for targeted UA delivery carriers to cancer cells while protecting normal cells from toxic drug activities.

From Red to Green Luminescence via Surface Functionalization. Effect of 2-(5-Mercaptothien-2-yl)-8-(thien-2-yl)-5-hexylthieno[3,4-c]pyrrole-4,6-dione Ligands on the Photoluminescence of Alloyed Ag-In-Zn-S Nanocrystals.

A semiconducting molecule containing a thiol anchor group, namely 2-(5-mercaptothien-2-yl)-8-(thien-2-yl)-5-hexylthieno[3,4-c]pyrrole-4,6-dione (abbreviated as D-A-D-SH), was designed, synthesized, and used as a ligand in nonstoichiometric quaternary nanocrystals of composition Ag1.0In3.1Zn1.0S4.0(S6.1) to give an inorganic/organic hybrid. Detailed NMR studies indicate that D-A-D-SH ligands are present in two coordination spheres in the organic part of the hybrid: (i) inner in which the ligand molecules form direct bonds with the nanocrystal surface and (ii) outer in which the ligand molecules do not form direct bonds with the inorganic core. Exchange of the initial ligands (stearic acid and 1-aminooctadecane) for D-A-D-SH induces a distinct change of the photoluminescence. Efficient red luminescence of nanocrystals capped with initial ligands (λmax = 720 nm, quantum yield = 67%) is totally quenched and green luminescence characteristic of the ligand appears (λmax = 508 nm, quantum yield = 10%). This change of the photoluminescence mechanism can be clarified by a combination of electrochemical and spectroscopic investigations. It can be demonstrated by cyclic voltammetry that new states appear in the hybrid as a consequence of D-A-D-SH binding to the nanocrystals surface. These states are located below the nanocrystal LUMO and above its HOMO, respectively. They are concurrent to deeper donor and acceptor states governing the red luminescence. As a result, energy transfer from the nanocrystal HOMO and LUMO levels to the ligand states takes place, leading to effective quenching of the red luminescence and appearance of the green one.

Rhenium(VII) Compounds as Inorganic Precursors for the Synthesis of Organic Reaction Catalysts.

Rhenium is an element that exhibits a broad range of oxidation states. Synthesis paths of selected rhenium compounds in its seventh oxidation state, which are common precursors for organic reaction catalysts, were presented in this paper. Production technologies for copper perrhenate, aluminum perrhenate as well as the ammonia complex of cobalt perrhenate, are thoroughly described. An ion exchange method, based on Al or Cu metal ion sorption and subsequent elution by aqueous perrhenic acid solutions, was used to obtain perrhenates. The produced solutions were neutralized to afford the targeted aluminum perrhenate and copper perrhenate products in high purity. The developed technologies allow one to manage the wastes from the production of these perrhenates as most streams were recycled. Hexaamminecobalt(III) perrhenate was produced by a newly developed method enabling us to produce a high purity compound in a reaction of spent hexaamminecobalt(III) chloride solution with a perrhenic acid. All prepared compounds are the basis for precursor preparation in organic catalysis.

Highly Luminescent Ag-In-Zn-S Quaternary Nanocrystals: Growth Mechanism and Surface Chemistry Elucidation.

The presented research is focused on the synthesis of alloyed Ag-In-Zn-S colloidal nanocrystals from a mixture of simple metal precursors such as AgNO3, InCl3, zinc stearate combined with 1-dodecanethiol (DDT), 1-octadecene (ODE), and sulfur dissolved in oleylamine (OLA). In particular, the focus is on the effect of the solvent (ODE vs 1,2-dichlorobenzene (DCB)) and the type of sulfur precursor (S/OLA vs S/ n-octylamine (OCA)) on the metal precursors reactivates and on the chemical composition, crystal structure, and luminescent properties of the resulting nanocrystals. The replacement of ODE by DCB as a solvent lowers the reactivity of metal precursors and results in a 3-fold decrease of the photoluminescence quantum yields (Q.Y.) values (from 67% to 21%). This negative effect can be fully compensated by the use of S/OCA as a source of sulfur instead of S/OLA (Q.Y. increases from 21% to 64%). NMR studies of the isolated organic phase indicate that the S/OLA precursor generates two types of ligands being products of ( Z)-1-amino-9-octadecene (OLA) hydrogenation. These are "surface bound" 1-aminooctadecane (C18H37NH2) and crystal bound, i.e., alkyl chain covalently bound to the nanocrystal surface via surfacial sulfur (C18H37-NH-S crystal). Highly luminescent Ag-In-Zn-S nanocrystals exhibit a cation-enriched (predominantly indium) surface and are stabilized by a 1-aminooctadecane ligand, which shows more flexibility than OLA. These investigations were completed by hydrophilization of nanocrystals obtained via exchange of the primary ligands for 11-mercaptoundecanoic acid, (MUA) with only a 2-fold decrease of photoluminescence Q.Y. in the most successful case (from 67% to 31%). Finally, through ligand exchange, an electroactive inorganic/organic hybrid was obtained, namely, Ag-In-Zn-S/7-octyloxyphenazine-2-thiol, in which its organic part fully retained its electrochemical activity.