Cindy Gunawan

Cytotoxic origin of copper(II) oxide nanoparticles: Comparative studies with micron-sized particles, leachate, and metal salts

The work investigates the source of toxicity of copper oxide nanoparticles (CuO NPs) with respect to its leaching characteristic and speciation. Complexation-mediated leaching of CuO NPs by amino acids was identified as the source of toxicity toward Escherichia coli, the model microorganism used in the current study. The leached copper-peptide complex induces a multiple-fold increase in intracellular reactive oxygen species generation and reduces the fractions of viable cells, resulting in the overall inhibition of biomass growth. The cytotoxicity of the complex leachate is however different from that of equivalent soluble copper salts (nitrates and sulfates). A pH-dependent copper speciation during the addition of copper salts gives rise to uncoordinated copper ions, which in turn result in greater toxicity and cell lysis, the latter of which was not observed for CuO NPs even at comparable pH. Since leaching did not occur with micrometer-sized CuO, no cytotoxicty effect was observed, thus highlighting the prominence of materials toxicity at the nanoscale.

Reversible Antimicrobial Photoswitching in Nanosilver

Nanosilver has emerged as one of the most commercialized nanomaterials, particularly as antimicrobial agents with interesting applications such as wound dressings, textiles, water and air purification, self-sterilizing polymer films, and bone implants. In comparison to bulk counterparts, nanosilver exhibits superior antimicrobial activity toward various microorganisms. Its reactivity is in part driven by a high specific surface area and enhanced surface electronic effects. Incorporation of silver nanoparticles into bacteria was recognized by the surface and intracellular uptake of Escherichia coli, which potentially results in the binding of silver to sulfur-containing membranes and cytoplasmic proteins. Exposure of E. coli and Staphylococcus aureus to dissolved silver ions affects the DNA replication ability as well as inactivates the expression of ribosomal subunit proteins and enzymes vital for adenosine 50-triphosphate (ATP) production. Microscopic studies revealed the condensation and concentration of DNA in the center of the cell and detachment of the cytoplasm membrane from the cell wall upon treatment with silver ions. It was further reported recently that the antimicrobial mechanism of silver nanoparticles was related to protein/membrane damage of E. coli but not to DNA damage. While the antimicrobial effect of nanosilver is widely recognized and has triggered extensive research interest, the ‘‘tuning’’ of its antimicrobial activity, to the best of our knowledge, has never been reported. This is important especially for applications involving direct antimicrobial interactions with human cells such as those in self-sterilizing

Nanoparticle–protein corona complexes govern the biological fates and functions of nanoparticles

Upon contact with plasma or other protein-containing biological fluids, the surface of nanoparticles is immediately decorated with proteins forming a biologically active protein corona. The biological fates and functions of nanoparticles are determined by physiological responses toward these nanoparticle-protein corona complexes as the effective biological unit of nanoparticles. In this article, we review representative studies on the effects of particle physicochemical characteristics along with the protein profiles in the biological medium on the formation of protein corona and importantly, how the dynamic nature and protein fingerprints of the formed corona govern the biological responses toward nanoparticles. The biological effects arising from the presence of protein corona can be both beneficial and unfavourable to the biomedical applications of nanoparticles. The protein corona-cell interactions open up the feasibility of targeted delivery and cell-specific uptake of therapeutic nanoparticles and in other circumstances, engineering of nanoparticles as adjuvants for vaccine development as well as mitigation of the unintentional cytotoxic effects of nanoparticles. On the other hand, the protein corona-cell interactions could induce rapid clearance of nanoparticles from in vivo circulation as well as activating unwanted inflammatory responses. Taken together, the knowledge on the formation and biological effects of protein corona enables tailored tuning of the physicochemical characteristics of nanoparticles, unique to their intended biological activity.

Cellular uptake and reactive oxygen species modulation of cerium oxide nanoparticles in human monocyte cell line U937

Cerium oxide nanoparticles (nanoceria) are promising materials for intracellular oxygen free radical scavenging providing a potential therapy for reactive oxygen species (ROS)-mediated inflammatory processes. In this study rhombohedral-shaped nanoceria were synthesized by flame spray pyrolysis with tuneable particle diameters between 3 and 94 nm by changing the liquid precursor flow rate. Monocytes and macrophages are major players in inflammatory processes as their production of ROS species has important downstream effects on cell signalling. Therefore, this study examined the ability of the nanoceria to be internalised by the human monocytic cell line, U937, and scavenge intracellular ROS. U937 cells activated in the presence of phorbol 12-myristate 13-acetate (PMA) were found to be more responsive to the nanoceria than U937 cells, which may not be surprising given the role of monocyte/macrophages in phagocytosing foreign material. The smaller particles were found to contain more crystal lattice defects with which to scavenge ROS, however a greater proportion of both the U937 and activated U937 cell populations responded to the larger particles. Hence all nanoceria particle sizes examined in this study were equally effective in scavenging intracellular ROS.

Induced Adaptation of Bacillus sp. to Antimicrobial Nanosilver

The natural ability of Bacillus sp. to adapt to nanosilver cytotoxicity upon prolonged exposure is reported for the first time. The combined adaptive effects of nanosilver resistance and enhanced growth are induced under various intensities of nanosilver-stimulated cellular oxidative stress, ranging from only minimal cellular redox imbalance to the lethal levels of cellular ROS stimulation. An important implication of the present work is that such adaptive effects lead to the ultimate domination of nanosilver-resistant Bacillus sp. in the microbiota, to which nanosilver cytotoxicity is continuously applied.

Cellular uptake and activity of heparin functionalised cerium oxide nanoparticles in monocytes

Cerium oxide nanoparticles (nanoceria) are effective in scavenging intracellular reactive oxygen species (ROS). In this study nanoceria synthesized by flame spray pyrolysis (dXRD = 12 nm) were functionalised with heparin via an organosilane linker, 3-aminopropyltriethoxysilane. Nanoceria were functionalised with approximately 130 heparin molecules per nanoparticle as determined by thermo gravimetric analysis. Heparin functionalised nanoceria were more effectively internalised by the human monocyte cell line, U937, and U937 cells that had been activated with phorbol 12 myristate 13-acetate (PMA) than bare nanoceria. The heparin functionalised nanoceria were also more effective in scavenging ROS than nanoceria in both activated and unactivated U937 cells. Heparin coupled nanoceria were found to be biologically active due to their ability to bind fibroblast growth factor 2 and signal through FGF receptor 1. Additionally, the heparin-coupled nanoceria, once internalised by the cells, were found to be degraded by 48 h. Together these data demonstrated that heparin enhanced the biological properties of nanoceria in terms of cellular uptake and ROS scavenging, while the nanoceria themselves were more effective at delivering heparin intracellularly than exposing cells to heparin in solution.

Challenges to Developing Methane Biofiltration for Coal Mine Ventilation Air: A Review

Coal mine methane is a significant greenhouse gas source as well as a potential lost energy resource if not effectively used. In recent years, mine ventilation air (MVA) capture and use has become a key element of research and development due to comparatively larger methane emissions by MVA than other coal mine sources. Technologies have been evaluated to treat the low methane concentrations in MVA such as thermal-based technologies or processing by biofiltration. This review initially considers the techniques available for treating the low methane concentrations encountered in MVA, after which it focuses on developments in biofiltration systems. Biofiltration represents a simple, energy-efficient, and cheap alternative to oxidize methane from MVA. Major factors influencing biofilter performance along with knowledge gaps in relation to its application to MVA are identified and discussed.

Submicron and nano formulations of titanium dioxide and zinc oxide stimulate unique cellular toxicological responses in the green microalga Chlamydomonas reinhardtii

The work investigates the eco-cytoxicity of submicron and nano TiO₂ and ZnO, arising from the unique interactions of freshwater microalga Chlamydomonas reinhardtii to soluble and undissolved components of the metal oxides. In a freshwater medium, submicron and nano TiO₂ exist as suspended aggregates with no-observable leaching. Submicron and nano ZnO undergo comparable concentration-dependent fractional leaching, and exist as dissolved zinc and aggregates of undissolved ZnO. Cellular internalisation of solid TiO₂ stimulates cellular ROS generation as an early stress response. The cellular redox imbalance was observed for both submicron and nano TiO₂ exposure, despite exhibiting benign effects on the alga proliferation (8-day EC50>100 mg TiO₂/L). Parallel exposure of C. reinhardtii to submicron and nano ZnO saw cellular uptake of both the leached zinc and solid ZnO and resulting in inhibition of the alga growth (8-day EC50≥0.01 mg ZnO/L). Despite the sensitivity, no zinc-induced cellular ROS generation was detected, even at 100 mg ZnO/L exposure. Taken together, the observations confront the generally accepted paradigm of cellular oxidative stress-mediated cytotoxicity of particles. The knowledge of speciation of particles and the corresponding stimulation of unique cellular responses and cytotoxicity is vital for assessment of the environmental implications of these materials.

Coal-packed methane biofilter for mitigation of green house gas emissions from coal mine ventilation air

Methane emitted by coal mine ventilation air (MVA) is a significant greenhouse gas. A mitigation strategy is the oxidation of methane to carbon dioxide, which is approximately twenty-one times less effective at global warming than methane on a mass-basis. The low non-combustible methane concentrations at high MVA flow rates call for a catalytic strategy of oxidation. A laboratory-scale coal-packed biofilter was designed and partially removed methane from humidified air at flow rates between 0.2 and 2.4 L min−1 at 30°C with nutrient solution added every three days. Methane oxidation was catalysed by a complex community of naturally-occurring microorganisms, with the most abundant member being identified by 16S rRNA gene sequence as belonging to the methanotrophic genus Methylocystis. Additional inoculation with a laboratory-grown culture of Methylosinus sporium, as investigated in a parallel run, only enhanced methane consumption during the initial 12 weeks. The greatest level of methane removal of 27.2±0.66 g methane m−3 empty bed h−1 was attained for the non-inoculated system, which was equivalent to removing 19.7±2.9% methane from an inlet concentration of 1% v/v at an inlet gas flow rate of 1.6 L min−1 (2.4 min empty bed residence time). These results show that low-cost coal packing holds promising potential as a suitable growth surface and contains methanotrophic microorganisms for the catalytic oxidative removal of methane.

Widespread and Indiscriminate Nanosilver Use: Genuine Potential for Microbial Resistance

In this era of increasing antibiotic resistance, the use of alternative antimicrobials such as silver has become more widespread. Superior antimicrobial activity has been provided through fabrication of silver nanoparticles or nanosilver (NAg), which imparts cytotoxic actions distinct from those of bulk silver. In the wake of the recent discoveries of bacterial resistance to NAg and its rising incorporation in medical and consumer goods such as wound dressings and dietary supplements, we argue that there is an urgent need to monitor the prevalence and spread of NAg microbial resistance. In this Perspective, we describe how the use of NAg in commercially available products facilitates prolonged microorganism exposure to bioavailable silver, which underpins the development of resistance. Furthermore, we advocate for a judicial approach toward NAg use in order to preserve its efficacy and to avoid environmental disruption.