Inhibition of α4ß1 Integrin Activity by Small Tellurium Compounds Regulates PD-L1 Expression and Enhances Antitumor Effects.

Various cancer treatment approaches that inhibit the activity of the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) axis, a key player in tumor immune evasion, have been developed. We show that the immunomodulatory small tellurium complexes AS101 (ammonium trichloro(dioxoethylene-o,o')tellurate) and SAS (octa-O-bis(R,R)-tartarate ditellurane) suppress PD-L1 expression in a variety of human and mouse malignant cells via the modulation of α4ß1 very late antigen-4 (VLA-4) integrin activity. Consequently, the expression of pAkt and its downstream effector pNFκB are inhibited. Additionally, SAS promotes the death of mouse malignant cells by activated syngeneic splenocytes or CD8+ T cells, preventing the development of chemoresistance in malignant cells. Moreover, AS101 and SAS may increase, at least in part, chemosensitivity through inhibition of the VLA-4/IL-10/PD-L1 pathway. Additionally, AS101 or SAS treatment of B16/F10 melanoma-bearing mice decreased tumor cell PD-L1 expression, leading to increased CD8+ T-cell infiltration into the tumors and tumor shrinkage. Combination treatment with an αPD-1 antibody and either tellurium compound significantly increased the antitumor efficacy of immunotherapy. Overall, VLA-4 integrin signaling is critical for tumor immune evasion and is a potential target for cancer treatment. Finally, AS101 or SAS, biologically active tellurium compounds, can effectively enhance the therapeutic efficacy of αPD-1-based cancer immunotherapy.

Antibacterial tellurium-containing polycarbonate drug carriers to eliminate intratumor bacteria for synergetic chemotherapy against colorectal cancer.

Intratumor microbes have attracted great attention in cancer research due to its influence on the tumorigenesis, progression and metastasis of cancer. However, the therapeutic strategies targeting intratumoral microbes are still in their infancy. Specific microorganisms, such as Fusobacterium nucleatum (F. nucleatum), are abundant in various cancer and always result in the CRC progression and chemotherapy resistance. Here, a combined anticancer and antibacterial therapeutic strategy is proposed to deliver antitumor drug to the tumors containing intratumor microbiota by the antibacerial polymeric drug carriers. We construct oral tellurium-containing drug carriers using a complex of tellurium-containing polycarbonate with cisplatin (PTE@CDDP). The results show that the particle size of the prepared nanoparticles could be maintained at about 105 nm in the digestive system environment, which is in line with the optimal particle size of oral nanomedicine. In vitro mechanism study indicates that the tellurium-containing polymers are highly effective in killing F.nucleatum through a membrane disruption mechanism. The pharmacokinetic experiments confirmed that PTE@CDDP has the potential function of enhancing the oral bioavailability of cisplatin. Both in vitro and in vivo studies show that PTE@CDDP could inhibit intratumor F.nucleatum and lead to a reduction in cell proliferation and inflammation in the tumor site. Together, the study identifies that the CDDP-loaded tellurium-containing nanoparticles have great potential for treating the F.nucleatum-promoted colorectal cancer (CRC) by combining intratumor microbiota modulation and chemotherapy. The synergistic therapeutic strategy provide new insight into treating various cancers combined with bacterial infection. STATEMENT OF SIGNIFICANCE: The synthesized antibacterial polymer was first employed to remodel the intratumor microbes in tumor microenvironment (TME). Moreover, it was the first report of tellurium-containing polymers against F.nucleatum and employed for treatment of the CRC. A convenient oral dosage form of cisplatin (CDDP)-loaded tellurium-containing nanoparticles (PTE@CDDP) was adopted here, and the synergistic antibacterial/chemotherapy effect occurred. The PTE@CDDP could quickly and completely eliminate F.nucleatum in a safe dose. In the CRC model, PTE@CDDP effectively reversed the inflammation level and even restored the intestinal barrier damaged by F.nucleatum. The ultrasensitive ROS-responsiveness of PTE@CDDP triggered the fast oxidation and efficient drug release of CDDP and thus a highly efficient apoptosis of the tumors. Therefore, the tellurium-containing polymers are expected to serve as novel antibacterial agents in vivo and have great potential in the F.nucleatum-associated cancers. The achievements provided new insight into treating CRC and other cancers combined with bacterial infection.

Comparative investigation of tellurium-doped transition metal nanoparticles (Zn, Sn, Mn): Unveiling their superior photocatalytic and antibacterial activity.

In this study, tellurium-doped and undoped metal oxide nanoparticles (NPs) (ZnO, Mn3O4, SnO2) are compared, and a practical method for their synthesis is presented. Nanocomposites were created using the coprecipitation process, and comparisons between the three material categories under study were made using a range of characterization methods. The produced materials were subjected to structural, morphological, elemental composition, and functional group analyses using XRD, FESEM in combination with EDS, and FTIR. The optical characteristics in terms of cutoff wavelength were evaluated using UV-visible spectroscopy. Catalyzing the breakdown of methylene blue (MB) dye, the isolated nanocomposites demonstrated very consistent behavior when utilized as catalysts. Regarding both doped and undoped ZnO NPs, the maximum percentage of degradation was found to be 98% when exposed to solar Escherichia coli and Staphylococcus aureus, which stand for gram-positive and gram-negative bacteria, respectively, and were chosen as model strains for both groups using the disk diffusion technique in the context of in vitro antibacterial testing. Doped and undoped ZnO NPs exhibited greater antibacterial efficacy, with significant inhibition zones measuring 31.5 and 37.8 mm, compared with other metal oxide NPs.

Increased resistance against tellurite is conferred by a mutation in the promoter region of uncommon tellurite resistance gene tehB in the ter-negative Shiga toxin-producing Escherichia coli O157:H7.

Resistance to potassium tellurite (PT) is an important indicator in isolating Shiga toxin-producing Escherichia coli (STEC) O157:H7 and other major STEC serogroups. Common resistance determinant genes are encoded in the ter gene cluster. We found an O157:H7 isolate that does not harbor ter but is resistant to PT. One nonsynonymous mutation was found in another PT resistance gene, tehA, through whole-genome sequence analyses. To elucidate the contribution of this mutation to PT resistance, complementation of tehA and the related gene tehB in isogenic strains and quantitative RT‒PCR were performed. The results indicated that the point mutation not only changed an amino acid of tehA, but also was positioned on a putative internal promoter of tehB and increased PT resistance by elevating tehB mRNA expression. Meanwhile, the amino acid change in tehA had negligible impact on the PT resistance. Comprehensive screening revealed that 2.3% of O157:H7 isolates in Japan did not harbor the ter gene cluster, but the same mutation in tehA was not found. These results suggested that PT resistance in E. coli can be enhanced through one mutational event even in ter-negative strains. IMPORTANCE: Selective agents are important for isolating Shiga toxin-producing Escherichia coli (STEC) because the undesirable growth of microflora should be inhibited. Potassium tellurite (PT) is a common selective agent for major STEC serotypes. In this study, we found a novel variant of PT resistance genes, tehAB, in STEC O157:H7. Molecular experiments clearly showed that one point mutation in a predicted internal promoter region of tehB upregulated the expression of the gene and consequently led to increased resistance to PT. Because tehAB genes are ubiquitous across E. coli, these results provide universal insight into PT resistance in this species.

Low-dose cadmium telluride quantum dots trigger M1 polarization in macrophages through mTOR-mediated transcription factor EB activation.

The increasing application of quantum dots (QDs) increases interactions with organisms. The inflammatory imbalance is a significant manifestation of immunotoxicity. Macrophages maintain inflammatory homeostasis. Using macrophages differentiated by phorbol 12-myristate 13-acetate-induced THP-1 cells as models, the study found that low-dose (5 µM) cadmium telluride QDs (CdTe-QDs) hindered monocyte-macrophage differentiation. CD11b is a surface marker of macrophage, and the addition of CdTe-QDs during induction resulted in a decrease in CD11b expression. Moreover, exposure of differentiated THP-1 macrophage (dTHP-1) to 5 µM CdTe-QDs led to the initiation of M1 polarization. This was indicated by the increased surface marker CD86 expression, along with elevated level of NF-κB and IL-1ß proteins. The potential mechanisms are being explored. The transcription factor EB (TFEB) plays a significant role in immune regulation and serves as a crucial regulator of the autophagic lysosomal pathway. After exposed to CdTe-QDs, TFEB activation-mediated autophagy and M1 polarization were observed to occur simultaneously in dTHP-1. The mTOR signaling pathway contributed to TFEB activation induced by CdTe-QDs. However, mTOR-independent activation of TFEB failed to promote M1 polarization. These results suggest that mTOR-TFEB is an advantageous target to enhance the biocompatibility of CdTe-QDs.

The tellurite resistance gene cluster of pathogenic bacteria and its effect on oxidative stress response.

Tellurite resistance gene clusters have been identified in numerous pathogenic bacteria, including clinical isolates of Escherichia coli. The rareness of tellurium in host organisms and the noncontaminated environment raises a question about the true functionality of tellurite resistance gene clusters in pathogenesis and their possible contribution to bacterial fitness. The study aims to point out the beneficial effects of the tellurite resistance gene cluster of pathogenic bacteria to survive in ROS-rich environments. Here, we analysed the bacterial response to oxidative stress conditions with and without tellurite resistance gene clusters, which are composed of terWY1XY2Y3 and terZABCDEF genes. By measuring the levels of protein carbonylation, lipid peroxidation, and expression changes of oxidative stress genes upon oxidative stress, we propose a tellurite resistance gene cluster contribution to the elimination of oxidative damage, potentially increasing fitness and resistance to reactive oxygen species during macrophage attack. We have shown a different beneficial effect of various truncated versions of the tellurite resistance gene cluster on cell survival. The terBCDEF genes increased the survival of E. coli strain MC4100 by 13.21%, terW and terZABCDEF by 10.09%, and terWY1XY2Y3 and terZABCDEF by 25.57%, respectively. The ability to survive tellurite treatment is the most significant at 44.8% in wild clinical strain KL53 compared to laboratory strain E. coli MC4100 due to a complete wild-type plasmid presence.

Feathery Tellurium-Selenium Heterostructural Nanoadjuvant for the Synergistic Treatment of Bacterial Infections.

Antibacterial nanoagents with well-controlled structures are greatly desired to address the challenges of bacterial infections. In this study, a featherlike tellurium-selenium heterostructural nanoadjuvant (TeSe HNDs) was created. TeSe HNDs produced 1O2 and had high photothermal conversion efficiency when stimulated with 808 nm near-infrared (NIR) light. To create a synergistic treatment system (TeSe-ICG) with better photothermal and photodynamic capabilities, the photosensitizer indocyanine green (ICG) was then added. With a bactericidal rate of more than 99%, the NIR-mediated TeSe-ICG demonstrated an efficient bactericidal action against both Gram-negative bacteria (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus). In addition, TeSe-ICG was also effective in treating wound infections and could effectively promote wound healing without obvious toxic side effects. In conclusion, TeSe-ICG is expected to be a good candidate for the treatment of bacterial infections.

Nanofabrication of cobalt-tellurium using Allium sativum extract and its protective efficacy against H2O2-induced oxidative damage in HaCaT cells.

Allium sativum (A. sativum)is well known for its therapeutic and culinary uses. Because of their high medicinal properties, the clove extract was selected to synthesize cobalt-tellurium nanoparticles. The aim of the study was to evaluate the protective activity of the nanofabricated cobalt-tellurium using A. sativum (Co-Tel-As-NPs) against H2O2-induced oxidative damage in HaCaT cells. Synthesized Co-Tel-As-NPs were analyzed using UV-Visible spectroscopy, FT-IR, EDAX, XRD, DLS, and SEM. Various concentrations of Co-Tel-As-NPs were used as a pretreatment on HaCaT cells before H2O2 was added. Then, the cell viability and mitochondrial damage were compared between pretreated and untreated control cells using an array of assays (MTT, LDH, DAPI, MMP, and TEM), and the intracellular ROS, NO, and antioxidant enzyme production were examined. In the present research, Co-Tel-As-NPs at different concentrations (0.5, 1.0, 2.0, and 4.0µg/mL) were tested for toxicity using HaCaT cells. Furthermore, the effect of H2O2 on the viability of HaCaT cells was evaluated using the MTT assay for Co-Tel-As-NPs. Among those, Co-Tel-As-NPs at 4.0 µg/mL showed notable protection; with the same treatment, cell viability was discovered to be 91% and LDH leakage was also significantly decreased. Additionally, the measurement of mitochondrial membrane potential was significantly decreased by Co-Tel-As-NPs pretreatment against H2O2. The recovery of the condensed and fragmented nuclei brought about by the action of Co-Tel-As-NPs was identified using DAPI staining. TEM examination of the HaCaT cells revealed that the Co-Tel-As-NPs had a therapeutic effect against H2O2 keratinocyte damage.

Investigation into the Antibacterial Mechanism of Biogenic Tellurium Nanoparticles and Precursor Tellurite.

Antibacterial tellurium nanoparticles have the advantages of high activity and biocompatibility. Microbial synthesis of Te nanoparticles is not only a green technology but builds new ecological relationships in diverse environments. However, the antibacterial mechanism of Te nanoparticles is largely unclear. In this study, we report the bacterial synthesis of rod-shaped Te nanoparticles (BioTe) with high antibacterial activity against Escherichia coli. Morphology and permeability examination indicates that membrane damage is the primary reason for the antibacterial activity of BioTe, rather than ROS production and DNA damage. Moreover, a comparison of transcriptome and relative phenotypes reveals the difference in antibacterial mechanisms between BioTe and tellurite. Based on our evidence, we propose an antibacterial mode of rod-shaped BioTe, in which positively charged BioTe interact with the cell membrane through electrostatic attraction and then penetrate the membrane by using their sharp ends. In contrast, tellurite toxicity might be involved in sulfur metabolism.

Identification of hypervirulent Klebsiella pneumoniae carrying terW gene by MacConkey-potassium tellurite medium in the general population.

Objectives: To establish a MacConkey-potassium tellurium medium-based method for selectively culturing terW gene-positive Klebsiella pneumoniae (KP), to evaluate its performance and apply it to identifying particular clonal hypervirulent KP (hvKP) strains in epidemiological surveillance. Methods: The virulence genes, rmpA, iutA, and terW, were detected by PCR. The minimum inhibitory concentration of potassium tellurite of hvKP (rmpA +/ iutA +) and classical KP (rmpA - and iutA -) was determined using the agar dilution method. The MacConkey medium containing 4 µg/ml potassium tellurite was prepared and the performance in detecting terW + KP was evaluated, including an agreement with PCR and positive/negative predictive value. Fecal samples from healthy volunteers in Fujian were collected and cultured in the medium, then positive strains were identified using MALDI-TOF MS, antimicrobial susceptibility was tested by Kirby-Bauer assays, and virulence genes and capsular serotype genes were tested by PCR. Results: In KP isolated from clinical specimens (N = 198), the positive rate of terW was 37.9%, and the detection rate of terW in hvKP was significantly higher than that in classical KP (70.6% vs 13.3%). The potassium tellurite resistance levels of terW + (N = 75) and terW - (N = 55) KP were 8-128 µg/ml and <1-8 µg/ml, respectively, with significant differences. KP was selectively cultured on a MacConkey medium with 4 µg/ml potassium tellurite, and its agreement with PCR was good (Kappa=0.936), and the positive and negative percent agreement and positive and negative predictive values were 100% (75/75), 92.7% (51/55), 94.9% (75/79), and 100% (51/51), respectively. The prevalence of tellurite-resistant KP was 16.7% (86/516) in fecal samples from healthy volunteers, among which the positive rate of terW was 100% (86/86). The antimicrobial resistance characteristics of terW + KP showed no difference between healthy volunteers and inpatients. The most common capsular serotypes associated with high virulence were K1, K2, and K57. Conclusions: The MacConkey medium containing 4 µg/ml potassium tellurite could easily select and culture terW + KP in fecal samples with high sensitivity and specificity, which is a practical method for the epidemic surveillance of hvKP in the general population.

Biogenic synthesis of selenium and tellurium nanoparticles by marine bacteria and their biological activity.

Selenium (SeNPs) and tellurium nanoparticles (TeNPs) were synthesized by green technology using the three new bacterial marine isolates (strains PL 2476, AF 2469 and G 2451). Isolates were classified as Pseudoalteromonas shioyasakiensis according to 16S rRNA sequence analysis, morphological characteristics, and biochemical reactions. The bioreduction processes of isolates were studied in comparison with the previously described Alteromonas macleodii (strain 2328). All strains exhibited significant tolerance to selenite and tellurite up to 1000 µg/mL. A comparative analysis of the bioreduction processes of the isolates demonstrated that the strains have a high rate of reduction processes. Characterization of biogenic red SeNPs and black TeNPs using scanning electron microscopy (SEM), EDX analysis, Dynamic Light Scattering, and micro-Raman Spectroscopy revealed that all the isolates form stable spherical selenium and tellurium nanoparticles whose size as well as elemental composition depend on the producer strain. Nanoparticles of the smallest size (up to 100 nm) were observed only for strain PL 2476. Biogenic SeNPs and TeNPs were also characterized and tested for their antimicrobial, antifouling and cytotoxic activities. Significant antimicrobial activity was shown for nanoparticles at relatively high concentrations (500 and 1000 µg/mL), with the antimicrobial activity of TeNPs being more significant than SeNPs. In contrast, against cell cultures (breast cancer cells (SkBr3) and human dermal fibroblasts (HDF) SeNPs showed greater toxicity than tellurium nanoparticles. Studies have demonstrated the high antifouling effectiveness of selenium and tellurium nanoparticles when introduced into self-polishing coatings. According to the results obtained, the use of SeNPs and TeNPs as antifouling additives can reduce the concentration of leachable biocides used in coatings, reducing the pressure on the environment.

Selenium and tellurium in the development of novel small molecules and nanoparticles as cancer multidrug resistance reversal agents.

Selenium is an essential trace element that is crucial for cellular antioxidant defense against reactive oxygen species (ROS). Recently, many selenium-containing compounds have exhibited a wide spectrum of biological activities that make them promising scaffolds in Medicinal Chemistry, and, in particular, in the search for novel compounds with anticancer activity. Similarly, certain tellurium-containing compounds have also exhibited substantial biological activities. Here we provide an overview of the biological activities of seleno- and tellurocompounds including chemopreventive activity, antioxidant or pro-oxidant activity, modulation of the inflammatory processes, induction of apoptosis, modulation of autophagy, inhibition of multidrug efflux pumps such as P-gp, inhibition of cancer metastasis, selective targeting of tumors and enhancement of the cytotoxic activity of chemotherapeutic drugs, as well as overcoming tumor drug resistance. A review of the chemistry of the most relevant seleno- or tellurocompounds with activity against resistant cancers is also presented, paying attention to the synthesis of these compounds and to the preparation of bioactive selenium or tellurium nanoparticles. Based on these data, the use of these seleno- and tellurocompounds is a promising approach in the development of strategies that can drive forward the search for novel therapies or adjuvants of current therapies against drug-resistant cancers.

Hepatotoxicity-Related Oxidative Modifications of Thioredoxin 1/Peroxiredoxin 1 Induced by Different Cadmium-Based Quantum Dots.

The hepatotoxicity of cadmium-based quantum dots (Cd-QDs) has become the focus with their extensive applications in biomedicine. Previous reports have demonstrated that high oxidative stress and consequent redox imbalance play critical roles in their toxicity mechanisms. Intracellular antioxidant proteins, such as thioredoxin 1 (Trx1) and peroxiredoxin 1 (Prx1), could regulate redox homeostasis through thiol-disulfide exchange. Herein, we hypothesized that the excessive reactive oxygen species (ROS) induced by Cd-QD exposure affects the functions of Trx1 or Prx1, which further causes abnormal apoptosis of liver cells and hepatotoxicity. Thereby, three types of Cd-QDs, CdS, CdSe, and CdTe QDs, were selected for conducting an intensive study. Under the same conditions, the H2O2 level in the CdTe QD group was much higher than that of CdS or CdSe QDs, and it also corresponded to the higher hepatotoxicity. Mass spectrometry (MS) results show that excessive H2O2 leads to sulfonation modification (-SO3H) at the active sites of Trx1 (Cys32 and Cys35) and Prx1 (Cys52 and Cys173). The irreversible oxidative modifications broke their cross-linking with the apoptosis signal-regulating kinase 1 (ASK1), resulting in the release and activation of ASK1, and activation of the downstream JNK/p38 signaling finally promoted liver cell apoptosis. These results highlight the key effect of the high oxidative stress, which caused irreversible oxidative modifications of Trx1 and Prx1 in the mechanisms involved in Cd-QD-induced hepatotoxicity. This work provides a new perspective on the hepatotoxicity mechanisms of Cd-QDs and helps design safe and reliable Cd-containing nanoplatforms.

Te-Cefotaxime nanocomposites with restored antibiotic susceptibility and the LED light activated photothermal effect for rapid MRSA eradication.

The ever-growing antibiotic-resistant bacteria pose a huge threat to public health. Restoring the susceptibility of ineffective antibiotics by inorganic nanomaterials and combining the photothermal and antibiotic effects could be an optional strategy to combat this resistance. Here, cefotaxime (CTX) loaded tellurium nanoparticles (Te NPs) were fabricated to recover the antibacterial activity of the ineffective ß-lactam antibiotic CTX against methicillin-resistant Staphylococcus aureus (MRSA) and at the same time perform photothermal therapy under light-emitting diode (LED) irradiation with a wavelength in the range of 420-480 nm. The combination of 50 µg mL-1 Te-CTX NPs with 5 min LED irradiation produced a 30.4 °C temperature increase and killed 99% of MRSA in vitro. In vivo evaluation in mice revealed that Te-CTX NPs and LED irradiation accelerated the healing of MRSA infected wounds and presented biosafety. Furthermore, this combination accelerated glutathione oxidation and resulted in the disruption of the antioxidant defence system of MRSA. Such a synergistic antibiotic and photothermal therapy provides an innovative way for the treatment of antibiotic-resistant bacterial infections.

Synthesis of Tellurium Oxide (TeO2) Nanorods and Nanoflakes and Evaluation of Its Efficacy Against Leishmania major In Vitro and In Vivo.

PURPOSE: Today, the use of natural products and nanostructures has increased. Given the reports on beneficial effects of various organotellurane compounds on types of visceral leishmaniasis, we decided to investigate the effect of TeO2 NPs on Leishmania major (L. major). Tellurium can cause cell apoptosis in cancer cells without activating the caspase-pathway. METHODS: TeO2 NPs at first synthesized and the structure was checked by XRD, SEM and EDS tests. The cytotoxic effect of TeO2 NPs against L. major promastigotes, amastigotes and macrophages was assessed by MTT test or counting. The possible apoptosis of L. major by TeO2 NPs was evaluated by flow cytometry test. For in vivo assay, the lesions of infected BALB/c mice with L. major promastigotes were treated with TeO2 NPs, then the lesion size and survival rate were evaluated. RESULTS: The synthesis of TeO2 with tetragonal structure was confirmed by XRD. The combination of nanorods and nanoflakes and the presence of Te were proven by SEM and EDS, respectively. According the effects of nanoparticle on promastigotes and amastigotes, the IC50 values of TeO2 after 72 h of incubation were 15.13 and 52.22 µg/ml, respectively. TeO2 NPs induced apoptosis in about 41% of promastigotes. The ulcer greatly healed and survival rate was higher in treated mice compared to those in control group. CONCLUSION: Based on the data, favorable anti-leishmanial properties were observed by using TeO2 NPs. TeO2 NPs have cytotoxic impacts on L. major promastigotes and amastigotes in vitro and in vivo and may be regarded as a therapy option.

Effects of Substitution on Cytotoxicity of Diphenyl Ditelluride in Cultured Vascular Endothelial Cells.

Among organic-inorganic hybrid molecules consisting of organic structure(s) and metal(s), only few studies are available on the cytotoxicity of nucleophilic molecules. In the present study, we investigated the cytotoxicity of a nucleophilic organotellurium compound, diphenyl ditelluride (DPDTe), using a cell culture system. DPDTe exhibited strong cytotoxicity against vascular endothelial cells and fibroblasts along with high intracellular accumulation but showed no cytotoxicity and had less accumulation in vascular smooth muscle cells and renal epithelial cells. The cytotoxicity of DPDTe decreased when intramolecular tellurium atoms were replaced with selenium or sulfur atoms. Electronic state analysis revealed that the electron density between tellurium atoms in DPDTe was much lower than those between selenium atoms of diphenyl diselenide and sulfur atoms of diphenyl disulfide. Moreover, diphenyl telluride did not accumulate and exhibit cytotoxicity. The cytotoxicity of DPDTe was also affected by substitution. p-Dimethoxy-DPDTe showed higher cytotoxicity, but p-dichloro-DPDTe and p-methyl-DPDTe showed lower cytotoxicity than that of DPDTe. The subcellular distribution of the compounds revealed that the compounds with stronger cytotoxicity showed higher accumulation rates in the mitochondria. Our findings suggest that the electronic state of tellurium atoms in DPDTe play an important role in accumulation and distribution of DPDTe in cultured cells. The present study supports the hypothesis that nucleophilic organometallic compounds, as well as electrophilic organometallic compounds, exhibit cytotoxicity by particular mechanisms.

The role of cysteine in tellurate reduction and toxicity.

The tellurium oxyanion tellurate is toxic to living organisms even at low concentrations; however, its mechanism of toxicity is poorly understood. Here, we show that exposure of Escherichia coli K-12 to tellurate results in reduction to elemental tellurium (Te[0]) and the formation of intracellular reactive oxygen species (ROS). Toxicity assays performed with E. coli indicated that pre-oxidation of the intracellular thiol pools increases cellular resistance to tellurate-suggesting that intracellular thiols are important in tellurate toxicity. X-ray absorption spectroscopy experiments demonstrated that cysteine reduces tellurate to elemental tellurium. This redox reaction was found to generate superoxide anions. These results indicate that tellurate reduction to Te(0) by cysteine is a source of ROS in the cytoplasm of tellurate-exposed cells.

Thermodynamic and kinetic insights into the interactions between functionalized CdTe quantum dots and human serum albumin: A surface plasmon resonance approach.

To explore in vivo application of quantum dots (QDs), it is essential to understand the dynamics and energetics of interactions between QDs and proteins. Here, surface plasmon resonance (SPR) and molecular docking were employed to investigate the kinetics and thermodynamics of interactions between human serum albumin (HSA) and CdTe QDs (~3 nm) functionalized with mercaptopropionic acid (MPA) or thioglycolic acid (TGA). Kinetic analysis showed that HSA-QD interactions involved transition-complex formation. Despite the structural similarities between MPA and TGA, the [HSA-CdTe@TGA]‡ formation by association of free HSA and QDs demanded 70% more energy and higher entropic gain (Ea-TGA‡= 65.10 and T∆Sa-TGA‡= 28.62 kJ mol-1) than the formation of [HSA-CdTe@MPA]‡ (Ea-MPA‡ = 38.13 and T∆Sa-MPA‡ = 0.53kJ mol-1). While the [HSA-CdTe@MPA]° dissociation required higher energy and lower entropy loss (Ed-MPA‡ = 49.96 and T∆Sd-MPA‡ = - 32.18kJ mol-1) than the [HSA-CdTe@TGA]° dissociation (Ed-TGA‡= 30.78 and T∆Sd-TGA‡= - 51.12 kJ mol-1). The stability of [HSA-QDs]° was independent of the temperature and functionalizing group. However, the enthalpic and entropic components were highly affected by the substitution of MPA (ΔH° = - 11.83 and TΔS° = 32.72 kJ mol-1) with TGA (ΔH° = 34.31 and TΔS° = 79.73 kJ mol-1). Furthermore, molecular docking results indicated that the metal site on the QDs contributes to the stabilization of [HSA-QDs]°. Therefore, differences in QD functionalization and surface coverage densities can alter the HSA-QD interaction, thus their application.

Carambola-like Bi2Te3 superstructures with enhanced photoabsorption for highly efficient photothermal therapy in the second near-infrared biowindow.

Photothermal therapy (PTT) stimulated by light in the second near-infrared (NIR-II) biowindow shows great superiorities in the penetration ability of tissue and maximum permissible exposure (MPE). Exploring new photothermal agents with good optical absorbance in the NIR-II region is highly desirable for efficient cancer therapy. Herein, we successfully prepare carambola-like bismuth telluride (Bi2Te3) superstructures modified with PEGylated phospholipid (Bi2Te3@PEG) for CT imaging-guided PTT in the NIR-II biowindow. Attributing to their superstructures, Bi2Te3@PEG exhibited enhanced photoabsorption with higher photothermal conversion efficiency (55.3% for 1064 nm) compared with that of Bi2Te3 nanoparticles. Furthermore, the good X-ray attenuation capacity of Bi endows Bi2Te3@PEG with an outstanding performance as computed tomography (CT) contrast agents. Bi2Te3@PEG superstructures have been confirmed to effectively eliminate tumor in vitro and in vivo with negligible long-term toxicities, offering them great potential to act as theranostic platforms for cancer diagnosis and treatment.

Anti-Pseudomonas aeruginosa biofilm activity of tellurium nanorods biosynthesized by cell lysate of Haloferax alexandrinus GUSF-1(KF796625).

Pseudomonas aeruginosa, an opportunistic human pathogen, is a major health concern as it grows as a biofilm and evades the host's immune defenses. Formation of biofilms on catheter and endotracheal tubes demands the development of biofilm-preventive (anti-biofilm) approaches and evaluation of nanomaterials as alternatives to antibiotics. The present study reports the successful biosynthesis of tellurium nanorods using cell lysate of Haloferax alexandrinus GUSF-1 (KF796625). The black particulate matter had absorption bands at 0.5 and 3.6 keV suggestive of elemental tellurium; showed x-ray diffraction peaks at 2θ values 24.50°, 28.74°, 38.99°, 43.13°, 50.23° and displayed a crystallite size of 36.99 nm. The black nanorods of tellurium were an average size of 40 nm × 7 nm, as observed in transmission electron microscopy. To our knowledge, the use of cell lysate of Haloferax alexandrinus GUSF-1 (KF796625) as a green route for the biosynthesis of tellurium nanorods with a Pseudomonas aeruginosa biofilm inhibiting capacity is novel to haloarchaea. At 50 µg mL-1, these tellurium nanorods exhibited 75.03% in-vitro reduction of biofilms of Pseudomonas aeruginosa ATCC 9027, comparable to that of ciprofloxacin, which is used in treatment of Pseudomonas infections. Further, the observed ability of these nanoparticles to inhibit the formation of Pseudomonas biofilms is worthy of future research perusal.