Cytotoxicity of Laser-Synthesized Nanoparticles of Elemental Bismuth.

High X-ray absorption combined with photothermal properties make bismuth nanoparticles (Bi NP) a promising agent for multimodal cancer theranostics. However, the synthesis of Bi NP by the "classical" chemical methods has numerous limitations, including potential toxicity of the produced nanomaterials. Here we studied in vitro toxicity of laser-synthesized Bi NP coated with Pluronic F-127 on mouse fibroblast cell line L929. The survival of L929 cells decreased linearly with increasing the concentration of Bi NP in a concentration range of 3-500 µg/ml; the LC50 value was 57 µg/ml. The unique combination of functional properties and moderate toxicity of the laser-synthesized Bi NP makes them a new promising platform for sensitization of multimodal cancer theranostics.

The cytotoxicity effect of bismuth oxide particles synthesized hydrothermally using different reaction temperatures in vitro.

INTRODUCTION: Bismuth oxide (Bi2O3) particles gained attention in preclinical research especially in medical imaging. Bismuth oxide with its long circulation time is an alternative to the current iodine contrast media which directly possesses high X-ray attenuation coefficient. Exploration of bismuth compound is hampered owing to challenges in synthesizing control for in vivo stability. MATERIALS AND METHODS: This study aimed are to characterize Bi2O3 particles synthesized at 60, 90 and 120 °C via hydrothermal method and investigated cytotoxicity of cell viability assay, cell morphology analysis, intracellular reactive oxygen species (ROS) assay and expression of ER stress genes by real-time PCR. RESULTS: Results indicated that the size of rod-shaped Bi2O3 particles increased with rising synthesizing temperatures. The cytotoxicity of Bi2O3 particles in Chang liver cells was size-dependent. Bigger-sized Bi2O3 particles resulted in lesser toxicity effects. mRNA expressions of GRP78 and C/EBP homologous protein (CHOP) were down-regulated in all treated Chang liver cells due to the increasing size of Bi2O3 particles. Bi2O3 particles synthesized at 120 °C was found to be less toxic than iodine. CONCLUSION: Data suggested that the response of Chang liver cells to Bi2O3 particle cytotoxicity has a significant relationship with its reaction temperatures. This outcome is important in hazard assessment of Bi2O3 particles as a new contrast media and provides better understanding in synthesizing control to enhance its biocompatibility.

Bioactive Bismuth Compounds: Is Their Toxicity a Barrier to Therapeutic Use?

Bismuth compounds are considered relatively non-toxic, with their low solubility in aqueous solutions (e.g., biological fluids) being the major contributing factor to this property. Bismuth derivatives are widely used for the treatment of peptic ulcers, functional dyspepsia, and chronic gastritis. Moreover, the properties of bismuth compounds have also been extensively explored in two main fields of action: antimicrobial and anticancer. Despite the clinical interest of bismuth-based drugs, several side effects have also been reported. In fact, excessive acute ingestion of bismuth, or abuse for an extended period of time, can lead to toxicity. However, evidence has demonstrated that the discontinuation of these compounds usually reverses their toxic effects. Notwithstanding, the continuously growing use of bismuth products suggests that it is indeed part of our environment and our daily lives, which urges a more in-depth review and investigation into its possible undesired activities. Therefore, this review aims to update the pharmaco-toxicological properties of bismuth compounds. A special focus will be given to in vitro, in vivo, and clinical studies exploring their toxicity.

Response mechanism of Chlamydomonas reinhardtii to nanoscale bismuth oxyiodide (nano-BiOI): Integrating analysis of mineral nutrient metabolism and metabolomics.

Nanoscale bismuth oxyiodide (nano-BiOI) is widely studied and applied in environmental applications and biomedical fields, with the consequence that it may be deposited into aquatic environments. However, the impact of nano-BiOI on aquatic ecosystems, especially freshwater microalga, remains limited. Herein, the nano-BiOI was synthesized and its response mechanism towards microalga Chlamydomonas reinhardtii was evaluated. Results showed that a low concentration of nano-BiOI (5 mg/L) could stimulate algal growth at the early stage of stress. With the increase in concentration, the growth rate of algal cells was inhibited and showed a dose effect. Intracellular reactive oxygen species (ROS) were significantly induced and accompanied by enhanced lipid peroxidation, decreased nonspecific esterase activity, and significantly upregulated glutathione S-transferase activity (GST) activity. Mineral nutrient metabolism analysis showed that nano-BiOI significantly interfered with the mineral nutrients of the algae. Non-targeted metabolomics identified 35 different metabolites (DEMs, 22 upregulated, and 13 downregulated) under 100 mg/L BiOI stress. Metabolic pathway analysis demonstrated that a high concentration of nano-BiOI significantly induced metabolic pathways related to amino acid biosynthesis, lipid biosynthesis, and glutathione biosynthesis, and significantly inhibited the sterol biosynthesis pathway. This finding will contribute to understanding the toxicological mechanisms of nano-BiOI on C. reinhardtii.

Unveiling the visible-light-driven photodegradation pathway and products toxicity of tetracycline in the system of Pt/BiVO4 nanosheets.

The antibiotics pollution has currently captured increasing concerns due to its potential hazards to the environment and human health. The development of efficient and viable techniques for the removal of antibiotics is one of the research hotspots in fields of wastewater treatment and pharmaceutical industry. Although the photodegradation of antibiotics is widely studied, the evolution and toxicity of degradation intermediates have been rarely documented. Herein, Pt nanoparticles (NPs) decorated BiVO4 nanosheets (Pt/BiVO4 NSs) that exhibit excellent tetracycline (TC) photodegradation activity and stability have been prepared. Especially, the TC degradation efficiency reaches ca. 88.5% after 60 min under visible light irradiation, which is superior to most of the metal loaded two-dimensional photocatalysts reported hitherto. The excellent photocatalytic activity is attributable to the enhanced light absorption capacity and charge separation efficiency in Pt/BiVO4 NSs. h+, •O2- and •OH are the main active species for TC degradation, resulting in three possible degradation pathways. Furthermore, we first verify that TC solutions treated by Pt/BiVO4 NSs are harmless to Escherichia coli K-12 and various bacteria in natural rivers, which would not stimulate Escherichia coli to produce antibiotics resistance genes (ARGs). This work develops an environmentally friendly photodegradation strategy using Pt/BiVO4 NSs with potentials for efficient remediation of antibiotics pollution in wastewater.

Bi/Se-Based Nanotherapeutics Sensitize CT Image-Guided Stereotactic Body Radiotherapy through Reprogramming the Microenvironment of Hepatocellular Carcinoma.

The particular characteristics of hypoxia, immune suppression in the tumor microenvironment, and the lack of accurate imaging guidance lead to the limited effects of stereotactic body radiotherapy (SBRT) in reducing the recurrence rate and mortality of hepatocellular carcinoma (HCC). This research developed a novel theranostic agent based on Bi/Se nanoparticles (NPs), synthesized by a simple reduction reaction method for in vivo CT image-guided SBRT sensitization in mice. After loading Lenvatinib (Len), the obtained Bi/Se-Len NPs had excellent performance in reversing hypoxia and the immune suppression status of HCC. In vivo CT imaging results uncovered that the radiotherapy (RT) area could be accurately labeled after the injection of Bi/Se-Len NPs. Under Len's unique and robust properties, in vivo treatment was then carried out upon injection of Bi/Se-Len NPs, achieving excellent RT sensitization effects in a mouse HCC model. Comprehensive tests and histological stains revealed that Bi/Se-Len NPs could reshape and normalize tumor blood vessels, reduce the hypoxic situation of the tumor, and upregulate tumor-infiltrating CD4+ and CD8+ T lymphocytes around the tumors. Our work highlights an excellent proposal of Bi/Se-Len NPs as theranostic nanoparticles for image-guided HCC radiotherapy.

Bismuth-based nanoparticles impair adipogenic differentiation of human adipose-derived mesenchymal stem cells.

Bismuth-based nanoparticles (BiNPs) have attracted attention for their potential biomedical applications. However, there is a lack of information concerning their interaction with biological systems. In this study, it was investigated the effect of physically synthesized BiNPs to human adipose-derived stem cells (ADSCs). We first evaluated the influence of BiNPs on cell viability, cell morphology, mitochondrial function and cell proliferation. Further, the impact of BiNPs on adipogenic differentiation was also explored. Cytotoxicity assays have demonstrated that BiNPs did not reduce relative cell viability of ADSC except at the highest tested concentration (345 µg/ml). Analysis of cell morphology performed by transmission electron microscopy confirmed that BiNPs induced cell damage only at a high concentration (302.24 µg/ml), equivalent to IC50 concentration. Moreover, BiNPs exposure increased the expression of the cell proliferation marker Ki-67 and the incorporation of the thymidine analogue EdU into cell DNA, suggesting that these nanoparticles could be stimulating ADSC proliferation. BiNPs also increased the mitochondrial membrane potential. Furthermore, BiNPs reduced ADSC adipogenic differentiation as measured by lipid droplet accumulation and mRNA expression levels of the specific adipogenesis biomarkers PPARγ, C/EPBɑ and FABP4. Thus, BiNPs affect the nonspecific (viability, proliferation and mitochondrial activity) and specific (adipogenesis) cellular mechanisms of ADSCs.

Bismuth subsalicylate incorporated in polycaprolactone-gelatin membranes by electrospinning to prevent bacterial colonization.

Periodontitis is a chronic, multifactorial, inflammatory disease characterized by the progressive destruction of the periodontal tissues. Guided tissue regeneration (GTR), involving the use of barrier membranes, is one of the most successful clinical procedures for periodontal therapy. Nevertheless, rapid degradation of the membranes and membrane-related infections are considered two of the major reasons for GTR clinical failure. Recently, integration of non-antibiotic, antimicrobial materials to the membranes has emerged as a novel strategy to face the bacterial infection challenge, without increasing bacterial resistance. In this sense, bismuth subsalicylate (BSS) is a non-antibiotic, metal-based antimicrobial agent effective against different bacterial strains, that has been long safely used in medical treatments. Thus, the aim of the present work was to fabricate fibrillar, non-rapidly bioresorbable, antibacterial GTR membranes composed of polycaprolactone (PCL), gelatin (Gel), and BSS as the antibacterial agent. PCL-G-BSS membranes with three different BSS concentrations (2 wt./v%, 4 wt./v%, and 6 wt./v%) were developed by electrospinning and their morphology, composition, water wettability, mechanical properties, Bi release and degradation rate were characterized. The Cytotoxicity of the membranes was studiedin vitrousing human osteoblasts (hFOB) and gingival fibroblasts (HGF-1), and their antibacterial activity was tested againstAggregatibacter actinomycetemcomitans, Escherichia coli, Porphyromonas gingivalisandStaphylococcus aureus.The membranes obtained exhibited adequate mechanical properties for clinical application, and appropriate degradation rates for allowing periodontal defects regeneration. The hFOB and HGF-1 cells displayed adequate viability when in contact with the lixiviated products from the membranes, and, in general, displayed antibacterial activity against the four bacteria strains tested. Thus, the PCL-G-BSS membranes showed to be appropriate as potential barrier membranes for periodontal GTR treatments.

Jointed Synchronous Photocatalytic Oxidation and Chromate Reduction Enabled by the Defect Distribution upon BiVO4: Mechanism Insight and Toxicity Assessment.

Exploring active and ecological materials for the restoration of complex pollution system is highly desired. This study presents a facile defect-tailoring strategy for combined pollutants purification with BiVO4 photocatalysis in which the jointed synchronous reaction of oxidation and reduction is integrated instead of the sequential reaction in two individual systems. XPS and EPR reveal that BiVO4 with a suitable oxygen vacancies (OVs) concentration and distribution exhibits superior photocatalytic activity under the coexistence of TC-HCl and Cr(VI) with Cr(VI) reduction efficiency increased by 71 times compared with the individual Cr(VI) system along with TC-HCl removal efficiency comparable to a single TC-HCl system. The mechanism of synchronous redox reactions mediated by surface OVs is revealed by comprehensive characterization together with reaction kinetic analysis, and the electronic band structure adjustment induced by the OVs variation is confirmed. Active species identification tests and intermediate product analysis confirm that singlet oxygen (1O2) accounts for the selective oxidation of TC-HCl, while electrons dominate the reduction of Cr(VI), under a coexistent environment. The influence of water quality parameters (e.g., pH, cations, anions, and organic substances) on the photocatalytic activity is investigated considering the complexity of the real aquatic environment. Importantly, toxicity assessment with Gram-negative strain E. coli as a model bacterium validates that the toxicity of the intermediates can be reduced to low or even ultralow levels. This work is dedicated to the mechanistic study of defect photocatalysis over BiVO4 and provides a jointed synchronous reaction system for combined pollutant purification.

Interactions of Non-steroidal Anti-inflammatory Drugs and Their Bismuth Analogues (BiNSAIDs) with Biological Membrane Mimics at Physiological pH.

Previous studies have demonstrated the potential for non-steroidal anti-inflammatory drugs (NSAIDs), in particular aspirin, to be used as chemopreventives for colorectal cancer; however, a range of unwanted gastrointestinal side effects limit their effectiveness. Due to the role of bismuth in the treatment of gastrointestinal disorders, it is hypothesized that bismuth-coordinated NSAIDs (BiNSAIDs) could be used to combat the gastrointestinal side effects of NSAIDs while still maintaining their chemopreventive potential. To further understand the biological activity of these compounds, the present study examined four NSAIDs, namely, tolfenamic acid (tolfH), aspirin (aspH), indomethacin (indoH), and mefenamic acid (mefH) and their analogous homoleptic BiNSAIDs ([Bi(L)3]n), to determine how these compounds interact with biological membrane mimics composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or a mixture of POPC and cholesterol. Electrical impedance spectroscopy studies revealed that each of the NSAIDs and BiNSAIDs influenced membrane conductance, suggesting that temporary pore formation may play a key role in the previously observed cytotoxicity of tolfH and Bi(tolf)3. Quartz crystal microbalance with dissipation monitoring showed that all the compounds were able to interact with membrane mimics composed of solely POPC or POPC/cholesterol. Finally, neutron reflectometry studies showed changes in membrane thickness and composition. The location of the compounds within the bilayer could not be determined with certainty; however, a complex interplay of interactions governs the location of small molecules, such as NSAIDs, within lipid membranes. The charged nature of the parent NSAIDs means that interactions with the polar headgroup region are most likely with larger hydrophobic sections, potentially leading to deeper penetration.

Cytotoxicity of bismuth nanoparticles in the murine macrophage cell line RAW 264.7.

A promising use of bismuth nanoparticles (BiNPs) for different biomedical applications leads to a search for the elucidation of their toxicity mechanisms, since toxicity studies are still at early stage. In the current study, cytotoxic effects of BiNPs produced by laser ablation in solution (LASiS) was investigated in the murine macrophage line RAW 264.7. The cells were exposed to 0.01-50 µg ml-1 of BiNPs for 24 and 48 h and then cytotoxicity assays were performed. Decrease of MTT conversion to formazan and of cell attachment were observed with no effects on cell proliferation. No loss of membrane integrity or significant changes of ROS and RNS levels were observed in exposed cells. Foremost, increased phagocytic activity and DNA repair foci occurred for cells exposed to BiNPs. These effects are important findings that must be considered in the case of biomedical application of BiNPs, since inappropriate macrophages activation and inactivation may lead to immunotoxicity. Bismuth nanoparticles (BiNPs) produced by laser ablation in solution and stabilized with BSA decrease enzyme-dependent MTT conversion to formazan and increase phagocytic activity and DNA repair foci in murine macrophage line RAW 264.7 when exposed to 50 µg ml-1. These effects are findings that should be considered in the case of biomedical application of BiNPs, since inappropriate macrophages activation and inactivation may lead to immunotoxicity.

A Review on the Biodistribution, Pharmacokinetics and Toxicity of Bismuth-Based Nanomaterials.

Here, bismuth-based nanomaterials (Bi-based NMs) are introduced as promising theranostic agents to enhance image contrast as well as for the therapeutic gain for numerous diseases. However, understanding the interaction of such novel developed nanoparticles (NPs) within a biological environment is a requisite for the translation of any promising agent from the lab bench to the clinic. This interaction delineates the fate of NPs after circulation in the body. In an ideal setting, a nano-based therapeutic agent should be eliminated via the renal clearance pathway, meanwhile it should have specific targeting to a diseased organ to reach an effective dose and also to overcome off-targeting. Due to their clearance pathway, biodistribution patterns and pharmacokinetics (PK), Bi-based NMs have been found to play a determinative role to pass clinical approval and they have been investigated extensively in vivo to date. In this review, we expansively discuss the possible toxicity induced by Bi-based NMs on cells or organs, as well as biodistribution profiles, PK and the clearance pathways in animal models. A low cytotoxicity of Bi-based NMs has been found in vitro and in vivo, and along with their long-term biodistribution and proper renal clearance in animal models, the translation of Bi-based NMs to the clinic as a useful novel theranostic agent is promising to improve numerous medical applications.

Bismuth chelate as a contrast agent for X-ray computed tomography.

BACKGROUNDS: Due to the unexpected side effects of the iodinated contrast agents, novel contrast agents for X-ray computed tomography (CT) imaging are urgently needed. Nanoparticles made by heavy metal elements are often employed, such as gold and bismuth. These nanoparticles have the advantages of long in vivo circulation time and tumor targeted ability. However, due to the long residence time in vivo, these nanoparticles may bring unexpected toxicity and, the preparation methods of these nanoparticles are complicated and time-consuming. METHODS: In this investigation, a small molecular bismuth chelate using diethylenetriaminepentaacetic acid (DPTA) as the chelating agent was proposed to be an ideal CT contrast agent. RESULTS: The preparation method is easy and cost-effective. Moreover, the bismuth agent show better CT imaging for kidney than iohexol in the aspect of improved CT values. Up to 500 µM, the bismuth agent show negligible toxicity to L02 cells and negligible hemolysis. And, the bismuth agent did not induce detectable morphology changes to the main organs of the mice after intravenously repeated administration at a high dose of 250 mg/kg. The pharmacokinetics of the bismuth agent follows the first-order elimination kinetics and, it has a short half-life time of 0.602 h. The rapid clearance from the body promised its excellent biocompatibility. CONCLUSIONS: This bismuth agent may serve as a potential candidate for developing novel contrast agent for CT imaging in clinical applications.

Autophagic blockage by bismuth sulfide nanoparticles inhibits migration and invasion of HepG2 cells.

The biological effects of nanoparticles are of great importance for the in-depth understanding of safety issues in biomedical applications. Induction of autophagy is a cellular response after nanoparticle exposure. Bismuth sulfide nanoparticles (Bi2S3 NPs) are often used as a CT contrast agent because of their excellent photoelectric conversion ability. Yet there has been no previous detailed study other than a cell toxicity assessment. In this study, three types of Bi2S3 NPs with different shapes (Bi2S3 nano rods (BSNR), hollow microsphere Bi2S3 NPs (BSHS) and urchin-like hollow microsphere Bi2S3 NPs (ULBSHS)) were used to evaluatecytotoxicity, autophagy induction, cell migration and invasion in human hepatocellular carcinoma cells (HepG2). Results showed that all three Bi2S3 NPs lead to blockage in autophagic flux, causing p62 protein accumulation. The cell death caused by these Bi2S3 NPs is proved to be autophagy related, rather than related to apoptosis. Moreover, Bi2S3 NPs can reduce the migration and invasion in HepG2 cells in an autophagy-dependent manner. ULBSHS is the most cytotoxic among three Bi2S3 NPs and has the best tumor metastasis suppression. These results demonstrated that, even with relatively low toxicity of Bi2S3 NPs, autophagy blockage may still substantially influence cell fate and thus significantly impact their biomedical applications, and that surface topography is a key factor regulating their biological response.

Solvothermal synthesis of facet-dependent BiVO4 photocatalyst with enhanced visible-light-driven photocatalytic degradation of organic pollutant: assessment of toxicity by zebrafish embryo.

The BiVO4 photocatalyst plays a very important role in photocatalytic reactions attributed to its unique crystalline structure, size, morphology and surface area. Herein, we report a facet-dependent monoclinic scheelite BiVO4 (m-BiVO4) photocatalyst with uniform truncated square (18 sided) hexagonal bipyramidal shape synthesized by a template-free and surfactant-free solvothermal method using ethylene glycol solvent under cost-effective and mild reactions. The structural, morphological and optical properties of the m-BiVO4 photocatalyst are widely characterized. The photocatalytic activity of the m-BiVO4 photocatalyst is tested towards 20 ppm methylene blue (MB) dye aqueous solution as a pollutant model under visible light irradiation. Enhanced visible-light driven photoactivity with dye degradation efficiency of approx. 91% at a rate of 0.388 × 10-2 min-1 is obtained, presumably due to the presence of high-active (040) facets. Zebrafish embryo toxicity test of treated MB dye solution reveals the degradation and toxicity reduction of the MB dye. Moreover, the recycling experiment validates that the m-BiVO4 photocatalyst has a great structural stability with reliable performance. This work may provide a lucid and expedient strategy to synthesize highly crystalline (040) facet-dependent semiconductor photocatalyst toward dye degradation and obviously industrial wastewater remediation.

Integration of Fe3O4 with Bi2S3 for Multi-Modality Tumor Theranostics.

The combination of reactive oxygen species (ROS)-induced chemodynamic therapy (CDT) and photothermal therapy (PTT) holds a promising application prospect for their superb anticancer efficiency. Herein, we created a novel Fe3O4@polydopamine (PDA)@bovine serum albumin (BSA)-Bi2S3 composite as a theranostic agent, by chemically linking the Fe3O4@PDA with BSA-Bi2S3 via the amidation between the carboxyl groups of BSA and the amino groups of PDA. In this formulation, the Fe3O4 NPs could not only work as a mimetic peroxidase to trigger Fenton reactions of the innate H2O2 in the tumor and generate highly cytotoxic hydroxyl radicals (•OH) to induce tumor apoptosis but also serve as the magnetic resonance imaging (MRI) contrast agent to afford the precise cancer diagnosis. Meanwhile, the PDA could prevent the oxidization of Fe3O4, thus supporting the long-term Fenton reactions and the tumor apoptosis in the tumor. The Bi2S3 component exhibits excellent photothermal transducing performance and computed tomography (CT) imaging capacity. In addition, the PDA and Bi2S3 endow the Fe3O4@PDA@BSA-Bi2S3 composite with an excellent photothermal transforming ability which could lead to tumor hyperthermia. All of these merits play the synergism with the tumor microenvironment and qualify the Fe3O4@PDA@BSA-Bi2S3 NPs for a competent agent in the MRI/CT-monitored enhanced PTT/CDT synergistic therapy. Findings in this research will evoke new interests in future cancer therapeutic strategies based on biocompatible nanomaterials.

Biocompatible, Crystalline, and Amorphous Bismuth-Based Metal-Organic Frameworks for Drug Delivery.

The synthetic flexibility of metal-organic frameworks (MOFs) with high loading capacities and biocompatibility makes them ideal candidates as drug delivery systems (DDSs). Here, we report the use of CAU-7, a biocompatible bismuth-based MOF, for the delivery of two cancer drugs, sodium dichloroacetate (DCA) and α-cyano-4-hydroxycinnamic acid (α-CHC). We achieved loadings of 33 and 9 wt % for DCA and α-CHC, respectively. Interestingly, CAU-7 showed a gradual release of the drugs, achieving a release time of up to 17 days for DCA and 31 days for α-CHC. We then performed mechanical and thermal amorphization processes to attempt to delay the delivery of guest molecules even more. With the thermal treatment, we were able to achieve an outstanding 32% slower release of α-CHC from the thermally treated CAU-7. Using in vitro studies and endocytosis inhibitors, confocal microscopy, and fluorescence-activated cell sorting, we also demonstrated that CAU-7 was successfully internalized by cancer cells, partially avoiding lysosome degradation. Finally, we showed that CAU-7 loaded either with DCA or α-CHC had a higher therapeutic efficiency compared with the free drug approach, making CAU-7 a great option for biomedical application.

Recoverable Bismuth-Based Microrobots: Capture, Transport, and On-Demand Release of Heavy Metals and an Anticancer Drug in Confined Spaces.

Self-propelled microrobots are seen as the next step of micro- and nanotechnology. The biomedical and environmental applications of these robots in the real world need their motion in the confined environments, such as in veins or spaces between the grains of soil. Here, self-propelled trilayer microrobots have been prepared using electrodeposition techniques, coupling unique properties of green bismuth (Bi) with a layered crystal structure, magnetic nickel (Ni), and a catalytic platinum (Pt) layer. These Bi-based microrobots are investigated as active self-propelled platforms that can load, transfer, and release both doxorubicin (DOX), as a widely used anticancer drug, and arsenic (As) and chromium (Cr), as hazardous heavy metals. The significantly high loading capability for such variable cargoes is due to the high surface area provided by the rhombohedral layered crystal structure of bismuth, as well as the defects introduced through the oxide layer formed on the surface of bismuth. The drug release is based on an ultrafast electroreductive mechanism in which the electron injection into microrobots and consequently into the loaded objects causes an electrostatic repulsion between them and thus an ultrafast release of the loaded cargos. Remarkably, we have presented magnetic control of the Bi-based microrobots inside a microfluidic system equipped with an electrochemical setup as a proof-of-concept to demonstrate (i) heavy metals/DOX loading, (ii) a targeted transport system, (iii) the on-demand release mechanism, and (iv) the recovery of the robots for further usage.

Cytotoxicity of biologically synthesised bismuth nanoparticles against HT-29 cell line.

This study was purposed to examine the cytotoxicity and functions of biologically synthesised bismuth nanoparticles (Bi NPs) produced by Delftia sp. SFG on human colon adenocarcinoma cell line of HT-29. The structural properties of Bi NPs were investigated using transmission electron microscopy, energy dispersive X-ray, and X-ray diffraction techniques. The cytotoxic effects of Bi NPs were analysed using flow cytometry cell apoptosis while western blot analyses were applied to analyse the cleaved caspase-3 expression. Oxidative stress (OS) damage was determined using the measurement of the glutathione (GSH) and malondialdehyde (MDA) levels and antioxidant activity of superoxide dismutase (SOD) and catalase (CAT) levels. The half maximal inhibitory concentration (IC50) value of Bi NPs was measured to be 28.7 ± 1.4 µg/ml on HT-29 cell line. The viability of HT-29 represented a concentration-dependent pattern (5-80 µg/ml). The mode of Bi NPs induced apoptosis was found to be mainly related to late apoptosis or necrosis at IC50 concentration, without the effect on caspase-3 activities. Furthermore, Bi NPs reduced the GSH and increased the MDA levels and decreased the SOD and CAT activities. Taken together, biogenic Bi NPs induced cytotoxicity on HT-29 cell line through the activation of late apoptosis independent of caspase pathway and may enhance the OS biomarkers.

Impact of surface modification on the toxicity of zerovalent iron nanoparticles in aquatic and terrestrial organisms.

Nanoscale zerovalent iron (nZVI)-based materials are increasingly being applied in environmental remediation, thereby lead to their exposure to aquatic and terrestrial biota. However, little is known regarding the toxic effects of surface-modified nZVI on multiple species in the ecosystem. In this study, we systematically compared the toxicities of different forms of nZVIs, such as bare nZVI, carboxymethyl cellulose (CMC)-stabilized nZVI, tetrapolyphosphate (TPP)-coated nZVI and bismuth (Bi)-doped nZVI, on a range of aquatic and terrestrial organisms, including bacteria (Escherichia coli and Bacillus subtilis), plant (Arabidopsis thaliana), water flea (Daphnia magna) and earthworm (Eisenia fetida). The Bi- and CMC-nZVI induced adverse biological responses across all the test systems, except E. fetida, varying from cell death in E. coli and B. subtilis to inhibition of the physiological states in D. magna and A. thaliana. The particle characterization under exposure conditions indicated that the surface modification of nZVI played a significant role in their toxicities by changing their physicochemical properties. The underlying mechanisms by which nZVI induces toxicity might be a combination of oxidative stress and another mechanism such as cell membrane disruption, chlorosis and hypoxia. Overall, our findings could provide important implications for the development of environment-friendly nanomaterials and direct further ecotoxicological researches regarding interspecies exploration.