Prediction of size-selective permitted daily exposures for mineral oil mist based on an in vitro study in different scenarios.

The incidence of DNA damage from exposure to specific types of metalworking fluids has been reported. In this research, size-selective permissible limits to prevent genotoxic damage in A549 cell lines exposed to two types of mineral oil were estimated for the first time using a benchmark dose approach and extrapolated to workers. The comet assay was performed based on Olive and Banath protocol to determine DNA damage. Then, the Benchmark Dose, the 95% lower bound confidence limit BMD, and the 95% upper-bound confidence limit BMD were determined using continuous response data. Finally, the four Benchmark Dose levels reported in the A549 cell line were extrapolated to the human population in occupational settings in two phases. This study showed when determining the permissible limits, the type used or unused, the type of injury, the organ affected in the body and the size of the particles should also be considered.

Cell toxicity assessment in co-treatment to metalworking fluids and vibration: an in vitro study of occupational exposure setting.

This study was designed to study dual risk of MWFs and vibration according to exposure simulation of selected industry. Air samples of two types MWFs were evaluated according to NIOSH 5026. Vibration acceleration exposure was assessed based on the ISO 8041:2005 standard. Cell treatment of both MWF air samples and vibration as the same as dual exposure to MWF airborne and vibration was assessed. There is a potency of nitrosamine formation in airborne samples of ethylamine containing MWF, while heterocyclic including bore is found in airborne bore containing MWF. DNA breaks caused by boron-containing MWF were higher than nitrosamine air samples. Oxidative stress production and chronic inflammation were highlighted in the response to cell treatments. The risk of cell toxicity in machining workers was evaluated at a level lower than the occupational exposure limit for MWFs and vibration.

Estimating the two graph dextran-stearic acid-spermine polymers based on iron oxide nanoparticles as carrier for gene delivery.

Non-viral gene carriers have shown noticeable potential in gene delivery because of limited side effects, biocompatibility, simplicity, and the ability to take advantage of electrostatic interactions. However, the low transfection rate of non-viral vectors under physiological conditions is controversial. This study aimed to decrease the transfection time using a static magnetic field. We used self-assembled cationic polysaccharides based on dextran-stearic acid-spermine (DSASP) conjugates associated with Fe3 O4 superparamagnetic nanoparticles to investigate their potential as gene carriers to promote the target delivery. Our findings illustrate that the magnetic nanoparticles are spherical with a positive surface charge and exhibit superparamagnetic behavior. The DSASP-pDNA/Fe3 O4 complexes offered a strong pDNA condensation, protection against DNase degradation, and significant cell viability in HEK 293T cells. Our results demonstrated that although conjugation of stearic acid could play a role in transfection efficiency, DSASP magnetic carriers with more spermine derivatives showed better affinity between the amphiphilic polymer and the negatively charged cell membrane.

Lung cell toxicity of co-exposure to airborne particulate matter and extremely low-frequency magnetic field.

Although the toxic effects of urban airborne particulate matter (PM) have been known on lung cells, there is less attention to co-exposure to PM and extremely low frequency magnetic (ELF-MF) in occupational settings. The present study investigated the influences of PM and ELF-MF co-exposure on toxicity in human lung cells (A549).In this case, total PM (TPM) was evaluated according to NIOSH-0500. The TPM SiO2 and metal contents were determined based on NIOSH-7602 and 7302, respectively. Besides, 900 mG ELF-MF exposure was simulated based on field measurements. The toxicity mechanisms were assessed by examining malondialdehyde, glutathione ratio, gene expression, and DNA strand breaks. Also, the toxicity indicators of the TPM samples were MDA generation, glutathione depletion, and DNA damage, and their impacts were analysed at doses below the LD50 (4 µg).In addition, gene expression of OGG1 and MTH1 was upregulated after TPM exposure at the lowest dose (2 µg). But ITPA was upregulated in the presence of ELF-MF. The co-exposure to TPM and ELF-MF decreased oxidative stress and DNA damage levels compared to a single exposure to TPM.Although the ELF-MF reduced toxicity in response to TPM, this reduction was not lower than the unexposed cells.

Detection of glioblastoma multiforme using quantitative molecular magnetic resonance imaging based on 5-aminolevulinic acid: in vitro and in vivo studies.

OBJECTIVES: We demonstrated a novel metabolic method based on sequential administration of 5-aminolevulinic acid (ALA) and iron supplement, and ferric ammonium citrate (FAC), for glioblastoma multiforme (GBM) detection using R2' and quantitative susceptibility mapping (QSM). MATERIALS AND METHODS: Intra-cellular iron accumulation in glioblastoma cells treated with ALA and/or FAC was measured. Cell phantoms containing glioblastoma cells and Wistar rats bearing C6 glioblastoma were imaged using a 3 T MRI scanner after sequential administration of ALA and FAC. The relaxivity and QSM analysis were performed on the images. RESULTS: The intra-cellular iron deposition was significantly higher in the glioma cells with sequential treatment of ALA and FAC for 6 h compared to those treated with the controls. The relaxivity and magnetic susceptibility values of the glioblastoma cells and rat brain tumors treated with ALA + FAC (115 ± 5 s-1 for R2', and 0.1 ± 0.02 ppm for magnetic susceptibility) were significantly higher than those treated with the controls (55 ± 18 (FAC), 45 ± 15 (ALA) s-1 for R2', p < 0.05, and 0.03 ± 0.03 (FAC), 0.02 ± 0.02 (ALA) ppm for magnetic susceptibility, p < 0.05). DISCUSSION: Sequential administration of ALA and iron supplements increases the iron deposition in glioblastoma cells, enabling clinical 3 T MRI to detect GBM using R2' or QSM.

Carbon dots doped by nitrogen and sulfur for dual-mode colorimetric and fluorometric determination of Fe3+ and histidine and intracellular imaging of Fe3+ in living cells.

The first dual-modality highly intensive fluorescent and colorimetric nanoprobe for Fe3+ ions and histidine is reported. The carbon dots doped by nitrogen and sulfur (N,S-CDs) prepared by the one-pot hydrothermal method have an excitation/emission wavelength of 320/420 nm with 56% quantum yield. N,S-CDs exhibit strong visible fluorescence with high stability at pH ~ 7.0. The fluorescence intensity of the N,S-CDs is quenched in the presence of Fe3+ ions which are recovered upon the addition of histidine. The addition of Fe3+ ions also induces a color change from yellow to red. Using colorimetric determination, Fe3+ and histidine exhibited linearity in the range 75-675 and 100-375 µmol L-1, respectively, while with fluorometric determinations the dynamic range was 0.1-275 and 0.1-3 µmol L-1 for Fe3+ and histidine, respectively. The limits of detection were 19 nmol L-1 and 0.03 µmol L-1 using fluorometry and 20 µmol L-1 and 24.2 µmol L-1 using colorimetry, for Fe3+ and histidine respectively. The relative standard deviations (n = 5) for Fe3+ (10 µmol L-1) and histidine (1 µmol L-1) using fluorometry were 4.6 and 7.3% and using colorimetry at 100 µmol L-1 of Fe3+ and 150 µmol L-1 of histidine were 3.2 and 5.6%, respectively. The developed fluorometric method was applied for the determination of Fe3+ and histidine in various foods and biological fluid samples as well as intracellular imaging of iron. The accuracy of the method for iron determination was confirmed by the analysis of certified reference materials (wheat flour, tomato leaves, and whole milk powder) and quality control materials (whole milk powder, serum, and urine), whereas for histidine, the accuracy was determined by recovery experiment and independent analysis. Good recovery values in ranges of 92-96% and 94-98% were achieved for Fe3+ and histidine, respectively. Graphical abstract.

DNA effects of low level occupational exposure to extremely low frequency electromagnetic fields (50/60 Hz).

AIMS: Exposure to extremely low frequency magnetic fields (ELF-MF) occurs from natural and artificial sources. Although ELF-MF has been classified as a suspected humans carcinogen agent by the International Agency for Research on Cancer, little is known of the effects of ELF-MF at lower exposure levels of the recommended range. In the present study, DNA damage in the peripheral blood cells of power line workers was investigated. MATERIALS AND METHODS: Occupational exposure to ELF-MF in a power plant was measured using the National Institute for Occupational Safety and Health (NIOSH) manual. Single-strand breaks (SSBs) in DNA were evaluated in 29 male utility workers as the exposed population and 28 male support personnel as the control subjects using the comet assay. Effects of ELF-MF on subjects were evaluated using DNA percent in tails, tail length, olive length, and tail moment. RESULTS: Occupational exposure levels to ELF-MF in the utility workers were less than the threshold limit values (TLV) recommended by the American Conference of Government Industrial Hygienist (ACGIH). The median value of the magnetic field at the working sites was 0.85 µT. Induction of DNA damage was observed for the exposed workers compared with the controls. Olive length, tail moment, and tail DNA percent increased significantly (p < 0.05) in the utility workers. CONCLUSIONS: Exposure to ELF-MF at levels less than the ACGIH exposure limit can produce DNA strand breaks.

Effect of precipitating agent, N2 gas, extract volume and pH on the magnetic properties of magnetite nanoparticles by green synthesis from aqueous pomegranate peel extract.

Superparamagnetic nanoparticles (SPMNPs) have attracted considerable attention in biomedicine, particularly magnetic hyperthermia for cancer treatment. However, the development of efficient and eco-friendly methods for synthesizing SPMNPs remains a challenge. This study reports on a green synthesis approach for SPMNPs using pomegranate peel extract as a stabilizing agent. The effects of various synthesis parameters, including the type of precipitating agent (NH3 and NaOH), N2 gas, extract volume, and pH, were systematically investigated with regard to the size, morphology, and magnetic properties of the nanoparticles. The results showed that reducing the volume of the extract increased the saturation magnetization of the nanoparticles. N2 gas was found to be essential in preventing the oxidation of the nanoparticles. The type of precipitating agent also affected the size and magnetization of the nanoparticles, with NaOH leading to the synthesis of SPMNPs with higher magnetization (∼4 times) compared to NH3. Additionally, nanoparticles synthesized at pH 10 exhibited higher magnetization than those synthesized at pH 8 and 12. In conclusion, the optimized synthesis conditions significantly affected the magnetization and stability of SPMNPs. These nanoparticles are suitable for use in magnetic nanofluid hyperthermia applications.

Intrinsic dual emissive insulin capped Au/Ag nanoclusters as single ratiometric nanoprobe for reversible detection of pH and temperature and cell imaging.

pH and temperature are two important characteristics in cells and the environment. These, not only in the well-done regulation of cell functions but also in diagnosis and treatment, have a key role. Protein-protected bimetallic nanoclusters are abundantly used in the building of biosensors. However, insulin-stabilized Au-Ag nanoclusters with dual intrinsic emission have not been investigated yet. In this work, Dual emissive insulin templated Au-Ag nanocluster (Ins(Au/Ag)NCs) were first synthesized in a simple and green one-put manner. The two emission wavelengths of, as-prepared NCs centered at 410 and 630 nm, excited in one excitation wavelength (330 nm). These two emission peaks were assigned to the di-Tyrosine cross-linked formation and bimetallic nanoclusters respectively. Further analysis displayed that each emission band of Ins(Au/Ag)NCs responded to one variable whilst another peak remained constant; For blue and red emission wavelengths, pH dependency and thermo-responsibility were observed respectively. As-prepared nanoprobe with the intrinsic dual emissive feature was used for ratiometric determination of these parameters, each with a discrete response from another. The linear range of 6.0-9.0 for pH and 1 to 71 °C for temperature was obtained, which comprises the physiological range of pH and temperature and afforded intracellular sensing and imaging capability. As-prepared NCs probe show excellent biocompatibility and cell membrane permeability, and so were successfully applied as direct ratiometric pH and temperature probes in HeLa and HFF cells. More interestingly, this dual emissive nanoprobe is capable of distinguishing cancer cells from normal ones.

Molecular dynamic simulation reveals the inhibiting impact of Rhein on wild-type and P29S-mutated Rac1.

Ras-related C3 botulinum toxin substrate 1 (Rac1) is a small GTPase belonging to the Rho family. It acts as a binary molecular switch regulating several cellular functions, including cell adhesion and migration. Malfunctions due to the P29S mutation in Rac1 increase the stability of the activated form of Rac1. This sustained activation can drive aberrant cellular processes associated with cancer, such as cell proliferation, survival, and migration. Therefore, finding an inhibitor that can inhibit the mutant form of the protein is very important. Rhein, a natural compound with diverse pharmacological properties, has been studied in relation to Rac1. However, specific interactions between Rhein and Rac1 have not been examined. In this study, we investigated the potential of Rhein, a natural compound, as an inhibitor of two forms of Rac1: the wild type and the P29S mutation, using molecular dynamics simulations. Results indicated that the P29S mutation led to structural changes in the Rac1 protein, which resulted in greater accessibility of the Rhein to the active site. In addition, the binding energy of Rhein to mutant Rac1 was more negative than the native protein. Therefore, it seems that the Rhein has a better inhibitory effect on the P29S-mutated form of the Rac1 protein.

Bioelectrocatalytic Activity of One-Dimensional Porous Pt Nanoribbons for Efficient Inhibition of Tumor Growth and Metastasis.

Designing and synthesizing one-dimensional porous Pt nanocrystals with unique optical, electrocatalytic, and theranostic properties are gaining lots of attention, especially to overcome the challenges of tumor recurrence and resistance to platinum-based chemotherapy. Herein, we represented an interesting report of a one-step and facile strategy for synthesizing multifunctional one-dimensional (1D) porous Pt nanoribbons (PtNRBs) with highly efficient therapeutic effects on cancer cells based on inherent electrocatalytic activity. The critical point in the formation of luminescent porous PtNRBs was the use of human hemoglobin (Hb) as a shape-regulating, stabilizing, and reducing agent with facet-specific domains on which fluorescent platinum nanoclusters at first are aggregated by aggregation-induced emission phenomena (AIE) and then crystallized into contact and penetration twins, as intermediate products, followed by shaping of the final luminescent porous ribbon nanomaterials, owing to oriented attachment association via the Ostwald ripening mechanism. From a medical point of view, the key strategy for effective cancer therapy occured via using low-dosage ethanol in the presence of electroactive porous PtNRBs based on intracellular ethanol oxidation-mediated reactive oxygen species (ROS) generation. The role of heme groups of Hb, as electrocatalytically active centers, was successfully demonstrated in both kinetically controlled anisotropic growth of NRBs for slowing down the reduction of Pt(II) followed by oligomerization of Pt(II)-Hb complexes via platinophilic interactions as well as electrocatalytic ethanol oxidation for therapy. Interestingly, hyaluronic acid-targeted (HA) Hb-PtNRB in the presence of low-dose ethanol caused extraordinary arrest of tumor growth and metastasis with no recurrence even after the treatment course stopped, which caused elongation of tumor-bearing mice survival. HA/Hb-PtNRB was completely biocompatible and exhibited high tumor-targeting efficacy for fluorescent imaging of breast tumors. Therefore, the synergistic electrocatalytic activity of PtNRBs is presented as an efficient and safe cancer theranostic method for the first time.

Polyethylenimine-based iron oxide nanoparticles enhance cisplatin toxicity in ovarian cancer cells in the presence of a static magnetic field.

Background: Drug resistance in cancer cells is a major concern in chemotherapy. Cisplatin (CIS) is one of the most effective chemotherapeutics for ovarian cancer. Here, we investigated an experimental approach to increase CIS cytotoxicity and overcome cell resistance using nanoparticle-based combination treatments. Methods: Polyethylenimine (PEI)-based magnetic iron oxide nanocomplexes were used for drug delivery in genetically matched CIS-resistant (A2780/CP) and -sensitive (A2780) ovarian cancer cells in the presence of a 20 mT static magnetic field. Magnetic nanoparticles (MNPs) were synthesized and bonded to PEI cationic polymers to form binary complexes (PM). The binding of CIS to the PM binary complexes resulted in the formation of ternary complexes PM/C (PEI-MNP/CIS) and PMC (PEI-MNP-CIS). Results: CIS cytotoxicity increased at different concentrations of CIS and PEI in all binary and ternary delivery systems over time. Additionally, CIS induced cell cycle arrest in the S and G2/M phases and reactive oxygen species production in both cell lines. Ternary complexes were more effective than binary complexes at promoting apoptosis in the treated cells. Conclusion: PEI-based magnetic nanocomplexes can be considered novel carriers for increasing CIS cytotoxicity and likely overcoming drug resistance of ovarian cancer cells.

Molecular properties of Ca2+ transport through TRPV2 channel: a molecular dynamics simulations study.

TRPV channels are a category of nonselective cation channels that are activated by heat and ligands and permeate monovalent and divalent ions. The mechanism of Ca2+ transfer through TRPV2 channel is not well known. Here, we investigated the reaction coordination and energy fluctuation of Ca2+ transition in TRPV2 channel by steered molecular dynamics (SMD) simulations and potential of mean force (PMF) calculation. Results showed that electrostatic interactions between Ca2+ and residues of the first and second gates had main roles in ions transfer through the channel. Also, we recognized important amino acids in this path. Moreover, results indicated that enter and exit of calcium ions need to overcome barrier energies in the first and second gates.Communicated by Ramaswamy H. Sarma.

Static and Electromagnetic Fields Differently Affect Proliferation and Cell Death Through Acid Enhancement of ROS Generation in Mesenchymal Stem Cells.

Magnetic fields remotely influence cellular homeostasis as a physical agent through the changes in cell physicochemical reactions. Magnetic fields affect cell fate, which may provide an important and interesting challenge in stem cell behaviors. Here, we investigated the effects of the static magnetic field (SMF, 20 mT) and electromagnetic field (EMF, 20 mT-50 Hz) on reactive oxygen species (ROS) production and the acidic pH conditions as stimuli to change cell cycle progression and cell death in mesenchymal stem cells. Results show that SMF, EMF, and their simultaneous (SMF+EMF) administration increase ROS and expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 2 (SOD2), and glutathione-S-transferase (GST) as an antioxidant defense system. Besides, intracellular pH (pHi) decreases in presence of either EMF or SMF+EMF, but not SMF. Decreased ROS content using ascorbic acid in these treatments leads to increased pH compared to the magnetic field treatments alone. Furthermore, each magnetic field has different effects on the cellular process of stem cells, including cell cycle, apoptosis and necrosis. Moreover, treatment by SMF enhances the cell viability after 24 h, while EMF or SMF+EMF decreases it. These observations indicate that fluctuations of ROS generation and acid enhancement during SMF and EMF treatments may reveal their beneficial and adverse effects on the molecular and cellular mechanisms involved in the growth, death, and differentiation of stem cells.

Structural Analysis and Conformational Dynamics of Short Helical Hyperphosphorylated Segments of Tau Protein (Sequence 254-290) in Alzheimer's Disease: A Molecular Dynamics Simulation Study.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose early diagnosis leads to a chance for successful treatment and decreases the side effects. Hyperphosphorylation of tau proteins is a pathological hallmark of AD that causes it to lose its attachment ability to the microtubules. Alteration of tau structure due to its hyperphosphorylation is an exciting challenge regarding AD treatments. Here, we aimed to examine the structural alterations of short helical segments of tau protein with one to three phosphorylated sites by molecular dynamics simulation. Results indicated that the interaction of two similar segments with three phosphorylated sites (P-Ser262, 285, and 289) formed a compact and more stable structure than the one phosphorylated site complex (P-Ser262). Moreover, due to the high dynamics of the P-Ser262 complex, several structures were made with different conformational dynamics, but there was only one stable cluster of the P-Ser262, 285, and 289 complex during simulation. It seems that the P-Ser262, 285, and 289 complex plays an important role in the formation of paired helical filaments (PHFs) by forming a stable dimer. Generally, it is important to identify how structural features of segments in tau protein change when the phosphorylated sites increase from one to three sites and their effects on the formation of PHFs for drug design and diagnostic biomarkers.

Health risk assessment of inhalation exposure to dry fogging of hydrogen peroxide in a dental clinic during the COVID-19 pandemic.

After the outbreak of COVID-19, many dental clinics use dry fogging of hydrogen peroxide (H2O2) to disinfect the air and surfaces. Inhalation of highly concentrated solutions of H2O2 may cause severe respiratory problems. This study aimed to estimate the health risk assessments of inhalation exposure to dry fogging of H2O2 in a dental clinic. This cross-sectional, descriptive-analytical study was performed to determine the inhalation exposure and health risk of 9 dental clinic staff with H2O2 in six rooms. Occupational exposure to H2O2 was assessed using the OSHA VI-6 method and a personal pump with the flow rate of 500 mL/min connected to the midget fritted-glass impinger containing 15 mL of TiOSO4 collecting solution. The health effects of H2O2 exposure were assessed using a respiratory symptoms questionnaire. The health risk assessment of inhaled exposure to H2O2 was also performed using the method provided by the Singapore occupational health department. The mean respiratory exposure of clinic staff to H2O2 was ranged from 1.3 to 2.83 ppm for six rooms which was above the limits recommended by international organizations. Dyspnea (44.4%), cough (33.3%), and nasal burning (22.2%) were the most prevalent health problems. The results also showed a medium risk for endodontics and surgery, and lower risk for periodontics, restorative care, orthodontics, and prosthetics. The results of this study indicate that when using an automated hydrogen peroxide-vapor fogger, calculating the spraying time based on room volume and using the rooms after 30 min of fogging is very important and can greatly reduce the risk ranking.

Effect of tea consumption on oxidative stress and expression of DNA repair genes among metal press workers exposed to occupational noise.

Several studies have shown that tea consumption is associated with beneficial effects on human health, which is mainly explained by the antioxidant properties of tea. However, evidence on the effect of nutrition interventions on oxidative stress in an occupational setting is limited. Therefore, the present study aimed to investigate the effect of tea consumption on oxidative stress in noise-exposed metal press workers. The study sample comprised 24 metal press workers and 24 age-matched control subjects. Metal press workers were assigned to the intervention group consisting of a glass of jujube tea and a portion of raisins per day for 4 weeks. Full-shift noise dosimetry was performed to measure noise exposure with average noise levels of 89.91 ± 2.92 dB for metal press workers and 61.54 ± 1.03 dB for control subjects. Elevated levels of baseline oxidative stress were observed in metal press workers compared with control subjects as indicated by significantly decreased levels of total antioxidant capacity (TAC) (P = 0.026) and total thiol groups (TTG) (P = 0.0001), whereas no significant difference was observed in case of malondialdehyde (MDA). Intervention with jujube tea and raisins in metal press workers led to a decrease of oxidative stress as displayed by increased levels of TAC and TTG (P = 0.0001) as well as decreased levels of MDA (P = 0.012). Moreover, the intervention significantly altered expression of repair genes in metal press workers as demonstrated by decreased levels of OGG1 (P = 0.0002) and ITPA (P = 0.009), whereas no significant difference was observed in case of MTH1. These data suggest that regular tea consumption may protect occupational noise-exposed subjects from oxidative damages.

Chromium speciation by isophthalic acid-doped polymer dots as sensitive and selective fluorescent probes.

Hexavalent chromium is a known carcinogen, among all species of chromium ions, for the respiratory tract in humans. In the present work, a new facile probe is developed for rapid and sensitive determination of Cr(VI) based on utilizing highly fluorescent conjugated poly[(9,9-dioctylfluorenyl-2,7-diyl)-alt-co-(1,4-benzo-(2,1',3) thiadiazole)] (PFBT) polymer dots (PDs). The PDs are easily functionalized by doping of isophthalic acid (IPA) into the target PDs during a single step preparation. The prepared PDs with an average diameter of 30 nm illustrated a strong fluorescence with an emission peak centered at 530 nm (photo-excited at 480 nm). The strong fluorescence of PDs is selectively and significantly quench with Cr(VI), while it does not change by Cr(III) ion and, thus, can facilitate a chromium speciation process. The proposed mechanism is an inner filter effect (IFE) mechanism, in which the absorption bands of Cr(IV) overlaps with the emission and excitation bands of the modified PDs. The prepared PDs revealed a good linear relationship from 0.1 to 1000 µmol L-1 for Cr(VI) with a detection limit of 0.03 µmol L-1, which further used to track the Cr distribution in water samples. Finally, the IPA-doped PDs with excellent optical properties, biocompatibility, and high quantum yield showed promising potential in tracking Cr species and specifying of different Cr ions inside the human cells, which opening a new door toward getting a better insight into the cell function and metabolism in the presence of heavy metal ions, and especially chromium ions.

Fluorescent Nanoclusters for Imaging of Cells/Stem Cells.

Imaging of cancer cells and cancer stem cells (CSCs) plays an important role in studying cell biology and tracking cancer development and metastasis. There is a wide interest in targeting cancer cells using fluorescent nanoclusters (NCs) capped in protein due to excellent cell viability and photostability, one-step synthesis route, large Stokes shift, good aqueous stability, and easy functionalization capability with long lifetime. Since CD44 is a CSC marker as well as a transmembrane receptor for hyaluronic acid (HA) and many other extracellular matrix (ECM) components, in this protocol, a biocompatible platform was synthesized by conjugation of HA onto luminescent platinum nanoclusters (Pt NCs) in human hemoglobin (Hb) (Hb/Pt NCs). This bioplatform could be used for specific imaging via an efficient targeting of CD44-overexpressing cancer cells and cancer stem cells.

Label free phosphate functionalized semiconducting polymer dots for detection of iron(III) and cytochrome c with application to apoptosis imaging.

We report on facile synthesis and characterization of phosphate-functionalized polymer dots (PDs) by doping tributyl phosphate (TBP) in a semiconducting polymer poly[9,9-dioctylfluorenyl-2,7-diyl)-co-1,4-benzo-{2,10-3}-thiadiazole)] (PFBT). Then, the prepared TBP@PFBT PDs were used to develop a very high sensitive probe for detection Fe3+, Cu2+ ions and Cytochrome c based on aggregation induced fluorescence off mechanism. The PDs exhibited a linear dynamic range for Fe3+ from 0.1 to 2 nM with a detection limit of 30 pM and for Cu2+ from 2.0 to 50.0 nM with a detection limit of 0.35 nM. Meanwhile, this probe showed a linear dynamic range for Cyt c from 175 to 1750 pM with a detection limit of 32.7 pM. The TBP@PFBT PDs is a simple, one-step, fast, non-invasive, label-free, and inexpensive probe that is capable of online apoptosis monitoring response to drugs with an ever-present opportunity to contribute in a variety of in-vitro and in-vivo biological applications. We also obtained sharp, specific 2D and 3D imaging results for early stage apoptosis in breast cancer cells. Moreover, this technique possesses the advantage of rapid determination of Fe3+ ion in biological or environmental samples. Importantly, this label-free assay provides short determination time of only a few min, easy operation and very low LOD allowing 100-4000 times increased in sensitivity over previously reported probes, together with high selectivity without need to using biorecognition elements like enzymes, antibodys and/or aptamers. Such excellent features make the TBP@PFBT PDs an excellent probe for successful apoptosis imaging in live cells.