Microplastic contamination in water and sediments of Mahanadi River, India: An assessment of ecological risk along rural-urban area.

Worldwide, environmental concerns about MPs pollution have increased. Microplastic contamination that pollutes the ocean is mostly caused by terrestrial transfer from close proximity locations. A study of MPs pollution near coastal locations becomes necessary to address the MPs transit, fate, and mitigation. In the current study MPs pollution in the surface water and sediment of the Mahanadi River estuary was assessed during Pre-MS and MS. The size, shape, and colour of the MPs were determined using a stereomicroscope, and the MPs polymer composition was identified by Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy. The mean concentration of MPs that were potentially discovered in water was 16.6 ± 5.2 and sediments 197.3 ± 5.4 during Pre-MS. In the MS observed mean abundance of MPs was 15.1 ± 5.4 in water and 164.6 ± 76.9 in sediments. The highest abundant size was smaller than 1 mm; the most prevalent shape were fibers followed by film and fragments; black and white was a prominent colour in water and sediments respectively. Polyesters (PEs), polyethylene (PE), polyvinyl chloride (PVC), polypropylene (PP), polyamide (PA), Polystyrene (PS), and Polycarbonates (PC) were found in the analysis of the chemical composition of MPs in water and sediments samples. The calculated PLI value shows pollution load at category I, with polymer hazard levels at categories III, IV, and V, indicating very high risk. The current research results show that river inflows and fishing-related actions are probably the main causes of MPs pollution.

Magnetically controlled drug delivery and hyperthermia effects of core-shell Cu@Mn3O4 nanoparticles towards cancer cells in vitro.

Recent increase in the integration of nanotechnology and nanosciences to the biomedical sector fetches the human wellness through the development of sustainable treatment methodologies for cancerous tumors at all stages of their initiation and progression. This involves the development of multifunctional theranostic probes that effectively support for the early cancer diagnosis, avoiding non-target cell toxicity, controlled and customized anticancer drug release etc. Therefore, to advance the field of nanotechnology-based sustainable cancer treatment, we fabricated and tested the efficacy of anticancer drug-loaded magnetic hybrid nanoparticles (NPs) towards in vitro cell culture systems. The developed conjugate of NPs was incorporated with the functions of both controlled drug delivery and heat-releasing ability using Mn3O4 (manganese oxide) magnetic core with Cu shell encapsulated within trimethyl chitosan (TMC) biopolymer. On characterization, the Cu@Mn3O4-TMC NPs were confirmed to have an approximate size of 130 nm with full agglomeration (as observed by the HRTEM) and crystal size of 92.95 ± 18.38 nm with tetragonal hausmannite phase for Mn3O4 spinel structure (XRD). Also, the UV-Vis and FTIR analysis provided the qualitative and quantitative effects of 5-fluororacil (5-Fu) anticancer drug loading (max 68 %) onto the Cu@Mn3O4-TMC NPs. The DLS analysis indicated for the occurrence of no significant changes to the particle size (around 100 nm) of Cu@Mn3O4-TMC due to the solution dispersion thereby confirming for the aqueous stability of developed NPs. In addition, the magnetization values of Cu@Mn3O4-TMC NPs were measured to be 34 emu/g and a blocking temperature of 42 K. Further tests of magnetic hyperthermia by the Cu@Mn3O4-TMC/5-Fu NPs provided that the heat-releasing capacity (% ΔT at 15 min) increases with that of increased frequency, i.e. 28 % (440 Hz) > 22.6 % (240 Hz) > 18 % (44 Hz), and the highest specific power loss (SPL) value observed to be 488 W/g for water. Moreover, the 5-Fu drug release studies indicate that the release is high at a pH of 5.2 and almost all the loaded drug is getting delivered under the influence of the external magnetic field (430 Hz) due to the influence of both Brownian-rotation and Néel relaxation heat-mediated mechanism. The pharmacokinetic drug release studies have suggested for the occurrence of more than one model, i.e. First-order, Higuchi (diffusion), and Korsemeyer-Peppas (non-Fickian), in addition to hyperthermia. Finally, the in vitro cell culture systems (MCF-7 cancer and MCF-10 non-cancer) helped to differentiate the physiological changes due to the effects of hyperthermia and 5-Fu drug individually and as a combination of both. The observed differences of cell viability losses among both cell types are measured and discussed with the expression of heat shock proteins (HSPs) by the MCF-10 cells as against the MCF-7 cancer cells. We believe that the results generated in this project can be helpful for the designing of new cancer therapeutic models with nominal adverse effects on healthy normal cells and thus paving a way for the treatment of cancer and other deadly diseases in a sustainable manner.

The Health Risk and Source Assessment of Polycyclic Aromatic Hydrocarbons (PAHs) in the Soil of Industrial Cities in India.

Industrial areas play an important role in the urban ecosystem. Industrial site environmental quality is linked to human health. Soil samples from two different cities in India, Jamshedpur and Amravati, were collected and analyzed to assess the sources of polycyclic aromatic hydrocarbons (PAHs) in industrial areas and their potential health risks. The total concentration of 16 PAHs in JSR (Jamshedpur) varied from 1662.90 to 10,879.20 ng/g, whereas the concentration ranged from 1456.22 to 5403.45 ng/g in the soil of AMT (Amravati). The PAHs in the samples were dominated by four-ring PAHs, followed by five-ring PAHs, and a small percentage of two-ring PAHs. The ILCR (incremental lifetime cancer risk) of the soil of Amravati was lower compared to that of Jamshedpur. The risk due to PAH exposure for children and adults was reported to be in the order of ingestion > dermal contact > inhalation while for adolescents it was dermal contact > ingestion > inhalation in Jamshedpur. In contrast, in the soil of Amravati, the PAH exposure path risk for children and adolescents were the same and showed the following order: dermal contact > ingestion > inhalation while for the adulthood age group, the order was ingestion > dermal contact > inhalation. The diagnostic ratio approach was used to assess the sources of PAHs in various environmental media. The PAH sources were mainly dominated by coal and petroleum/oil combustion. As both the study areas belong to industrial sites, the significant sources were industrial emissions, followed by traffic emissions, coal combustion for domestic livelihood, as well as due to the geographical location of the sampling sites. The results of this investigation provide novel information for contamination evaluation and human health risk assessment in PAH-contaminated sites in India.

Fabrication of magnetite nanomaterials employing novel ionic liquids for efficient oil spill cleanup.

The oil spill represents one of the most important pollution sources for marine environments, that occurs due to tanker collisions, ship accidents, and platforms. Several techniques are used for treating oil spill disasters including chemical, physical, and biochemical. The use of chemicals, magnetite nanomaterials (MNMs) in particular, is one of the most applied techniques used for oil spill remediation due to their low cost, fast remediation, and reusability. This work aims to synthesize and use new ionic liquids (ILs) for the modification of MNMs surfaces to enhance their performance for crude oil uptake. For that, octadecylamine (OA) was reacted with epichlorohydrin (EH), followed by reaction with either diethylenetriamine (DT), or tetraethylenepentamine (TP) to obtain corresponding amines, OADT, and OATP, respectively. The produced amines were quaternized using acetic acid (AA) forming corresponding ILs, OADT-IL, and OATP-IL. The obtained ILs, OADT-IL, and OATP-IL were applied for modification of magnetite nanomaterials (MNMs) surface to obtain the surface-modified MNMs, DT-MNMs, and TP-MNMs, respectively. The surface-modified MNMs were characterized using different techniques including Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), and contact angle. The efficacy of DT-MNMs, and TP-MNMs for heavy crude oil uptake (EMU) was evaluated. Further, the factors affecting on the crude oil uptake including MNMs: heavy crude oil ratio, and contact time were also evaluated. The data exhibited that, the EMU relatively declined as the ratio of DT-MNMs, and TP-MNMs decreased. Even at low MNMs:crude oil ratio (1:50), DT-MNMs, and TP-MNMs displayed EMU 87%, and 90%, respectively, which means 1 g of either DT-MNMs, or TP-MNMs can uptake 45 g, or 43.5 g, respectively. These values are high as compared with other studies that reported the use of MNMs for oil spill cleanup. Furthermore, the data indicated that the EMU increased as the contact time increased, and reached maximum EMU of 98% for both MNMs samples after 10 min.

Investigation of the Tribological Characteristics of Aluminum 6061-Reinforced Titanium Carbide Metal Matrix Composites.

The current trend in the materials engineering sector is to develop newer materials that can replace the existing materials in various engineering sectors in order to be more and more efficient. Therefore, the present research work is aimed at fabricating and determining the physical, mechanical, and dry sliding wear properties of titanium carbide (TiC)-reinforced aluminum alloy (Al6061) metal matrix composites (MMCs). For the study, the Al6061-TiC microparticle-reinforced composites were fabricated via the liquid metallurgy route through the stir casting method, where the reinforcement of the TiC particles into the Al6061 alloy matrix was added in the range of 0 to 8.0 wt.%, i.e., in the steps of 2.0 wt.%. The synthesis procedure followed the investigation of the various mechanical properties of Al6061-TiC MMCs, such as the density and structure, as well as mechanical and dry wear experimentation. The tests performed on the casted Al6061, as well as its TiC composites, were in harmony with ASTM standards. As per the experimental outcome, it can be confirmed that the increase in the weight percentage of TiC into the Al6061 alloy substantially increases the density, hardness, and tensile strength, at the expense of the percentage of elongation. In addition, the dry wear experiments, performed on a pin-on-disc tribometer, showed that the Al6061-TiC MMCs have superior wear-resistance properties, as compared to those of pure Al6061 alloy. Furthermore, optical micrograph (OM), powdered X-ray diffraction (XRD), energy dispersive spectroscopy (EDS), and scanning electron microscopy (SEM) analyses were employed for the developed Al6061-TiC MMCs before and after the fracture and wear test studies. From the overall analysis of the results, it can be observed that the Al6061-TiC composite material with higher TiC reinforcement displays superior mechanical characteristics.

Drug Release Profiles of Mitomycin C Encapsulated Quantum Dots-Chitosan Nanocarrier System for the Possible Treatment of Non-Muscle Invasive Bladder Cancer.

Nanotechnology-based drug delivery systems are an emerging technology for the targeted delivery of chemotherapeutic agents in cancer therapy with low/no toxicity to the non-cancer cells. With that view, the present work reports the synthesis, characterization, and testing of Mn:ZnS quantum dots (QDs) conjugated chitosan (CS)-based nanocarrier system encapsulated with Mitomycin C (MMC) drug. This fabricated nanocarrier, MMC@CS-Mn:ZnS, has been tested thoroughly for the drug loading capacity, drug encapsulation efficiency, and release properties at a fixed wavelength (358 nm) using a UV-Vis spectrophotometer. Followed by the physicochemical characterization, the cumulative drug release profiling data of MMC@CS-Mn:ZnS nanocarrier (at pH of 6.5, 6.8, 7.2, and 7.5) were investigated to have the highest release of 56.48% at pH 6.8, followed by 50.22%, 30.88%, and 10.75% at pH 7.2, 6.5, and 7.5, respectively. Additionally, the drug release studies were fitted to five different pharmacokinetic models including pesudo-first-order, pseudo-second-order, Higuchi, Hixson-Crowell, and Korsmeyers-Peppas models. From the analysis, the cumulative MMC release suits the Higuchi model well, revealing the diffusion-controlled mechanism involving the correlation of cumulative drug release proportional to the function square root of time at equilibrium, with the correlation coefficient values (R2) of 0.9849, 0.9604, 0.9783, and 0.7989 for drug release at pH 6.5, 6.8, 7.2, and 7.5, respectively. Based on the overall results analysis, the formulated nanocarrier system of MMC synergistically envisages the efficient delivery of chemotherapeutic agents to the target cancerous sites, able to sustain it for a longer time, etc. Consequently, the developed nanocarrier system has the capacity to improve the drug loading efficacy in combating the reoccurrence and progression of cancer in non-muscle invasive bladder diseases.

A One-Pot Three-Component Synthesis and Investigation of the In Vitro Mechanistic Anticancer Activity of Highly Functionalized Spirooxindole-Pyrrolidine Heterocyclic Hybrids.

With an aim to develop more effective and affordable anticancer agents possessing a unique mechanism of action, we designed and synthesized derivatives of spirooxindole-pyrrolidine heterocyclic hybrids in good yields through a one-pot three-component (3+2) cycloaddition strategy. The synthesized compounds were characterized thoroughly for the physicochemical properties by making use of FT-IR, NMR spectroscopy, and mass spectrometry. Further, these compounds have been evaluated for the influence of anticancer activity against HepG2 cells up to 200 µg/mL concentration. The highly active molecular scaffold was tested for the in-depth mechanistic studies, and it was found that the major pathway of cell death is apoptosis which occurs through the induction of reactive oxygen species followed by the involvement of caspases.

A Non-severe Coronavirus Disease 2019 Patient With Persistently High Interleukin-6 Level.

Interleukin 6 (IL-6) is one of the markers of immune system activation indicating existent infection and inflammation. We present here a case of a 55-year-old male COVID-19 patient with an unusual high level of interleukin 6 (IL-6). Further investigation revealed he had hepatocellular carcinoma (HCC) with underlying hepatitis B. He did not present with respiratory symptoms although a baseline chest x-ray showed changes, and the patient was categorized as Class 3A of COVID-19. Routine investigations proceeded with high-resolution computed tomography and IL-6 to monitor for progression to severe COVID-19. Notably, there was a high IL-6 level but other parameters did not show he was in severe COVID-19. In this report, we conclude that elevated IL-6 level in a COVID-19 patient is not necessarily associated with severe COVID-19.

Preparation, Characterization, and Radiolabeling of [68Ga]Ga-NODAGA-Pamidronic Acid: A Potential PET Bone Imaging Agent.

Early diagnosis of bone metastases is crucial to prevent skeletal-related events, and for that, the non-invasive techniques to diagnose bone metastases that make use of image-guided radiopharmaceuticals are being employed as an alternative to traditional biopsies. Hence, in the present work, we tested the efficacy of a gallium-68 (68Ga)-based compound as a radiopharmaceutical agent towards the bone imaging in positron emitting tomography (PET). For that, we prepared, thoroughly characterized, and radiolabeled [68Ga]Ga-NODAGA-pamidronic acid radiopharmaceutical, a 68Ga precursor for PET bone cancer imaging applications. The preparation of NODAGA-pamidronic acid was performed via the N-Hydroxysuccinimide (NHS) ester strategy and was characterized using liquid chromatography-mass spectrometry (LC-MS) and tandem mass spectrometry (MSn). The unreacted NODAGA chelator was separated using the ion-suppression reverse phase-high performance liquid chromatography (RP-HPLC) method, and the freeze-dried NODAGA-pamidronic acid was radiolabeled with 68Ga. The radiolabeling condition was found to be most optimum at a pH ranging from 4 to 4.5 and a temperature of above 60 °C. From previous work, we found that the pamidronic acid itself has a good bone binding affinity. Moreover, from the analysis of the results, the ionic structure of radiolabeled [68Ga]Ga-NODAGA-pamidronic acid has the ability to improve the blood clearance and may exert good renal excretion, enhance the bone-to-background ratio, and consequently the final image quality. This was reflected by both the in vitro bone binding assay and in vivo animal biodistribution presented in this research.

In vitro Mechanistic Exploration of Novel Spiropyrrolidine Heterocyclic Hybrids as Anticancer Agents.

Novel spiro acenaphthylene pyrrolo[1,2-b]isoquinoline/pyrrolidine hybrids have been achieved through Pictet-Spengler/Eschweiler-Clarke reactions depending on the substitution in the benzyl ring. The in vitro biological efficacy of N-methyl spiropyrrolidine derivatives toward different cancer and non-cancer cell lines revealed that these novel spiro heterocyclic hybrids induced cancer cell death at moderate concentrations, while slight reduction in non-cancer cell viability at the higher concentrations. The analysis of cancer cells proved that the major pathway of cell death is apoptosis and in addition, the role of caspases is confirmed by the appearance of fluorescent cells in microscopic images. Therefore, this study indicates a sustainable way of treating cancer cells by inducing apoptotic pathways and associated caspases, while simultaneously protecting the non-cancer cells.

Docking and in vitro molecular biology studies of p-anisidine-appended 1-hydroxy-2-acetonapthanone Schiff base lanthanum(iii) complexes.

A new series of lanthanum(iii) complexes was synthesized using a p-anisidine-appended 1-hydroxy-2-acetonapthanone (3) Schiff base and characterized via spectroscopic methods. The ligand was synthesized via sonication and the crystalline product was characterized using X-ray crystallography. The genotoxicity of the compound was assessed primarily by the bacterial reverse mutation (Ames) test and the in vitro mammalian chromosome aberration test; in both cases, the samarium complex 5 was found to be non-mutagenic. The anti-tumor activity of complexes 4, 5, and 6 was assayed against HeLa tumor cells and screened using the MTT assay. The IC50 value of complex 5 was found to be 34 ± 1.2 µg mL-1 and this compound exhibited superior activity towards the cells compared to 4 and 6. These results were further confirmed by Hoechst 33258 staining and AO/EI dual staining, which indicated that the cells underwent an apoptosis mechanism in a dose-dependent manner. The apoptosis was further confirmed by the formation of ladders in the DNA fragmentation assay, and the western blot analysis of complex 5 suggested that the cells underwent the caspase-3-dependent pathway with PARP cleavage. Furthermore, the docking studies of complex 5 with HSA showed that it was situated in a hydrophilic cavity held by the electrostatic attraction of four hydrogen-bonding interactions. PDB ID:1BNA binds with complex 5via strong π-π stacking interactions, which facilitate binding with the major grooves of DNA strands. The above-mentioned results illustrate that for complex 5, mitochondrion-mediated apoptosis occurs via caspase-3 activation. Complex 5 binds with DNA via intercalation because of S-phase cell cycle arrest in the HeLa cells.

D-Ring-Modified Analogues of Luotonin A with Reduced Planarity: Design, Synthesis, and Evaluation of Their Topoisomerase Inhibition-Associated Cytotoxicity.

A- and D-ring-modified luotonin-inspired heterocycles have been synthesized and were evaluated for their activity against the viability of four cancer cell lines in vitro, namely, MCF7, HCT116, JURKAT, and NCI-H460. The analysis of results indicated that two of the synthesized derivatives displayed good inhibition against the growth of the human colon cancer HCT116 cell line, with potencies lower than but in the same order of magnitude as camptothecin (CPT). These two luotonin analogues also showed an activity similar to that of the highly potent alkaloid CPT as inhibitors of topoisomerase I and also inhibited topoisomerase II. These results show that complete planarity is not a strict requirement for topoisomerase inhibition by luotonin-related compounds, paving the way to the design of analogues with improved solubility.

Design, Synthesis and In Vitro Mechanistic Investigation of Novel Hexacyclic Cage-Like Hybrid Heterocycles.

Novel hexacyclic cage-like hybrid heterocycles have been synthesized in excellent yields employing a relatively less explored non-stabilized azomethine ylides derived from acenaphthenequinone and tyrosine with functionalized dipolarophiles using [3 + 2] cycloaddition strategy. The synthesized hexacyclic cage-like hybrid heterocycles were characterized by spectroscopic analysis. Following the physical characterization, these cage-like hybrid heterocycles were tested for their biological activity by means of different cancer (A549 and Jurkat cells) and non-cancer (BRL-3A and PCS-130) in vitro cell culture systems. The results of the study under tested concentrations (up to 100 µM) indicated that these compounds are not affecting any viability to the cell growth of non-cancer cells, while providing significant anticancer activity against both of the cancer cells. Further analysis of in-depth mechanistic study for the cell death indicated that these compounds are exhibiting late apoptosis or early necrosis pathway to the cells where it is operated by the induction of caspases.

Biocompatible polylactic acid-reinforced nickel-arsenate composite: Studies of electrochemical conductivity, mechanical stability, and cell viability.

In continuation to our earlier work on nickel (Ni)-arsenate (As) composite, the current work deals with the electrical conductivity and mechanical resistivity of the same composite by means of its further reinforcement with the polylactic acid (PLA) polymer. For the PLA-Ni-As composite, we understand from the electrochemical studies that the conductivity is strongly influenced by the temperature and due to the presence of external electrolyte. The DC electrical conductivity approach used for the temperature dependency provided the information that the conductivity falls in the semiconductor zone ranging at 10-3 S cm-1, thereby indicating that it followed the Arrhenius equation. In addition, we found in terms of the mechanical properties that the PLA-Ni-As composite outperformed the plain, untreated Ni-As composite by reducing the activation energy. For the mechanical resistivity studies we found that the 25% PLA-loaded Ni-As material significantly improved the tensile strength and modulus, elongation at break %, impact properties and also the flexural strength and modulus as against the plain and other combinations due to enhanced interfacial interactions. The cell viability and proliferations studies tested against two different cell lines provided the information that the presence of polymer reduces the toxic response of arsenic material. From the cumulative analysis therefore, we indicate that the PLA-Ni-As composite can be a potential candidate to find its uses in the electrochemical and solar cells, in addition to automotive and aerospace industry.

Spirooxindole-pyrrolidine heterocyclic hybrids promotes apoptosis through activation of caspase-3.

A small library of spirooxindole-pyrrolidine hybrids have been synthesized for the first time in an ionic liquid, [bmim]Br in good to excellent yields employing a new class of non-stabilized azomethine ylides derived from isatin and tyrosine, a combination that has been rarely employed for the in situ generation of azomethine ylides using [3+2] cycloaddition strategy. Following the synthesis and characterization of the spirooxindole-pyrrolidine heterocyclic hybrids, they were tested for their anticancer activity as against the changes in the concentrations and time periods with different in vitro cell cultures containing cancer and non-cancer cells, where the results revealed for a potential therapeutic activity. Further analysis for the mechanism of cell death by the cancer cells indicated for the caspase-dependent apoptotic pathway, specifically mediated by caspase-3. Based on these results, it can be demonstrated that the synthesized spirooxindole-pyrrolidine hybrids may serve as one of the better therapeutic agents used for the treatment of malignant tumors.

The Role, Involvement and Function(s) of Interleukin-35 and Interleukin-37 in Disease Pathogenesis.

The recently identified cytokines-interleukin (IL)-35 and interleukin (IL)-37-have been described for their anti-inflammatory and immune-modulating actions in numerous inflammatory diseases, auto-immune disorders, malignancies, infectious diseases and sepsis. Either cytokine has been reported to be reduced and in some cases elevated and consequently contributed towards disease pathogenesis. In view of the recent advances in utilizing cytokine profiles for the development of biological macromolecules, beneficial in the management of certain intractable immune-mediated disorders, these recently characterized cytokines (IL-35 and IL-37) offer potential as reasonable targets for the discovery of novel immune-modulating anti-inflammatory therapies. A detailed comprehension of their sophisticated regulatory mechanisms and patterns of expression may provide unique opportunities for clinical application as highly selective and target specific therapeutic agents. This review seeks to summarize the recent advancements in discerning the dynamics, mechanisms, immunoregulatory and anti-inflammatory actions of IL-35 and IL-37 as they relate to disease pathogenesis.

Evaluation of porogen factors for the preparation of ion imprinted polymer monoliths used in mercury removal.

In the present study, ion imprinted polymer monoliths (IIPMs) were developed to overcome the limitations of ion imprinted polymer particles (IIPPs) used for the removal of Hg(II) ions from waste water samples. The adsorbents preparation, characterization and Hg(II) removal were very well reported. The IIPMs on porogen optimization was prepared using the molding technique with Hg(II) as a template ion, [2-(methacryloyloxy)ethyl]trimethylammonium cysteine (MAETC) as ligand, methacrylic acid (MAA) as functional monomer, ethylene glycol dimethacrylamide (EGDMA) as cross-linker, benzoyl peroxide as an initiator and methanol and acetonitrile as porogen in the polypropylene tube (drinking straw) as mold. The IIPMs prepared with higher volumes of porogen were indicated to have a good adsorption rate for the Hg(II) removal along with good water permeability and larger porosity as compared to a lower volume of porogen. The IIPMs prepared using the binary porogen were able to improve the porosity and surface area of the monolithic polymers as compared to the single porogen added IIPMs. Finally, we indicate from our analysis that the IIPM having the efficient capacity for the Hg(II) ions is easy to prepare, and has higher water permeability along with high porosity and high adsorption capacity and all these factors making it one of the suitable adsorbent for the successful removal of Hg(II) ions.

Highly functionalized pyrrolidine analogues: stereoselective synthesis and caspase-dependent apoptotic activity.

Novel spiropyrrolidine heterocyclic hybrids were synthesized for the first time in a sustainable fashion employing a 1,3-dipolar cycloaddition strategy to form a new class of azomethine ylides generated from tyrosine and acenaphthenequinone. Following their synthesis and characterization, these heterocyclic hybrids were tested for their anticancer activities by incubation at different concentrations and durations with different cancer and non-cancer cell cultures, and the results indicated a potential therapeutic activity. Further analysis of cancer cell death revealed that it occurred through a caspase-related apoptotic pathway, specifically mediated by caspase-3. These results demonstrated that the obtained spiropyrrolidine heterocyclic hybrids may be good hit compounds for the development of potential therapeutic agents for the treatment of malignant tumors.

Histological analysis of anti-cancer drug loaded, targeted Mn:ZnS quantum dots in metastatic lesions of 4T1 challenged mice.

5-Fluororaucil (5-FU) as anti-cancer drug was reported to induce thymidine synthase (TS) overexpression and cancer cell resistance. To improve its therapeutic efficacy and selective targeting, here we developed a targeted delivery system mediated by the active ligand-folate receptor chemistry to deliver the 5-FU drug selectively into the tumor microenvironment. The preparation was achieved by exploring chitosan (CS)-biopolymer based system with folic acid (FA)-conjugation. The 5-FU@FACS-Mn:ZnS quantum dots (QDs) based on the histological assessment conducted in the 4T1 challenged mice showed an improved tumor remission in the liver, spleen and lungs. The 5-FU@FACS-Mn:ZnS composite induced anti-proliferative properties in these organs as compared to the free 5-FU drug. Unlike the 5-FU@FACS-Mn:ZnS treated groups which showed some specific morphological changes such as cell shrinkage without obvious presence of adipocytes, the excised section of the tumor in the untreated control group and the free 5-FU drug treated group showed necrotic and degenerated cells; these cells are multifocally distributed in the tumor mass with evidence of widely distributed adipocytes within the tumor mass. These findings suggest that the 5-FU@FACS-Mn:ZnS composite has a superior role during the induction of apoptosis in the 4T1 cells as compared to the free 5-FU drug treated groups. The results of the study therefore suggest that the impregnation of 5-FU anti-cancer drug within the FACS-Mn:ZnS system significantly improves its selective targeting efficacy, in addition to improving the anti-proliferative properties and attenuate possible tumor resistances to the 5-FU drug. The work discusses about the anti-metastatic effects of folic acid-bound 5-Fluororacil loaded Mn:ZnS quantum dots towards 4T1 cell line proliferation in mice based on the histological analysis.

Thiolate-Capped CdSe/ZnS Core-Shell Quantum Dots for the Sensitive Detection of Glucose.

A semiconducting water-soluble core-shell quantum dots (QDs) system capped with thiolated ligand was used in this study for the sensitive detection of glucose in aqueous samples. The QDs selected are of CdSe-coated ZnS and were prepared in house based on a hot injection technique. The formation of ZnS shell at the outer surface of CdSe core was made via a specific process namely, SILAR (successive ionic layer adsorption and reaction). The distribution, morphology, and optical characteristics of the prepared core-shell QDs were assessed by transmission electron microscopy (TEM) and spectrofluorescence, respectively. From the analysis, the results show that the mean particle size of prepared QDs is in the range of 10-12 nm and that the optimum emission condition was displayed at 620 nm. Further, the prepared CdSe/ZnS core shell QDs were modified by means of a room temperature ligand-exchange method that involves six organic ligands, L-cysteine, L-histidine, thio-glycolic acid (TGA or mercapto-acetic acid, MAA), mercapto-propionic acid (MPA), mercapto-succinic acid (MSA), and mercapto-undecanoic acid (MUA). This process was chosen in order to maintain a very dense water solubilizing environment around the QDs surface. From the analysis, the results show that the CdSe/ZnS capped with TGA (CdSe/ZnS-TGA) exhibited the strongest fluorescence emission as compared to others; hence, it was tested further for the glucose detection after their treatment with glucose oxidase (GOx) and horseradish peroxidase (HRP) enzymes. Here in this study, the glucose detection is based on the fluorescence quenching effect of the QDs, which is correlated to the oxidative reactions occurred between the conjugated enzymes and glucose. From the analysis of results, it can be inferred that the resultant GOx:HRP/CdSe/ZnS-TGA QDs system can be a suitable platform for the fluorescence-based determination of glucose in the real samples.