Silver nanoparticles (AgNP) are known to penetrate into the brain and cause neuronal death. However, there is a paucity in studies examining the effect of AgNP on the resident immune cells of the brain, microglia. Given microglia are implicated in neurodegenerative disorders such as Parkinson’s disease (PD), it is important to examine how AgNPs affect microglial inflammation to fully assess AgNP neurotoxicity. In addition, understanding AgNP processing by microglia will allow better prediction of their long term bioreactivity. In the present study, the in vitro uptake and intracellular transformation of citrate-capped AgNPs by microglia, as well as their effects on microglial inflammation and related neurotoxicity were examined. Analytical microscopy demonstrated internalization and dissolution of AgNPs within microglia and formation of non-reactive silver sulphide (Ag₂S) on the surface of AgNPs. Furthermore, AgNP-treatment up-regulated microglial expression of the hydrogen sulphide (H₂S)-synthesizing enzyme cystathionine-γ-lyase (CSE). In addition, AgNPs showed significant anti-inflammatory effects, reducing lipopolysaccharide (LPS)-stimulated ROS, nitric oxide and TNFα production, which translated into reduced microglial toxicity towards dopaminergic neurons. Hence, the present results indicate that intracellular Ag₂S formation, resulting from CSE-mediated H₂S production in microglia, sequesters Ag⁺ ions released from AgNPs, significantly limiting their toxicity, concomitantly reducing microglial inflammation and related neurotoxicity.

Gold nanostars (AuNSs) are receiving increasing attention for their potential applications in bionanotechnology because of their unique optical properties related to their complex branched morphology. Their sharp features allow strong localized surface plasmon resonances, tunable in the near-infrared (NIR) region, and large enhancements of local electromagnetic fields. Here, the application of AuNSs in metal-enhanced fluorescence (MEF) in the NIR and second NIR (NIR-II) biological windows is explored for the first time. NIR/NIR-II fluorophores are incorporated onto monolayers of AuNSs with tunable plasmonic responses. Over 320-fold fluorescence enhancement is achieved in the NIR, confirming that AuNS substrates are promising NIR-MEF platforms for the development of ultrasensitive biosensing applications. Using fluorescence lifetime measurements to semiquantitatively deconvolute the excitation enhancement from emission enhancement, as well as modeling to simulate the electric field enhancement, we show that a combination of enhanced excitation and an increased radiative decay rate, accompanied by an increase in the quantum yield, contribute to the observed large enhancement. AuNSs with different morphological features exhibit significantly different excitation enhancements, indicating the important role of the particle morphology on the magnitude of electromagnetic field enhancement and the resulting enhancement factor. Importantly, enhancement factors of up to 50-fold are also achieved in the NIR-II region, suggesting that this system holds promise for the future development of bright probes for NIR/NIR-II biosensing and bioimaging.

Silver nanowires (AgNWs) are being developed for use in optoelectronics. However before widespread usage, it is crucial to determine their potential effects on human health. It is accepted that Ag nanoparticles (AgNPs) exert toxic effects by releasing Ag⁺ ions, but much less is known about whether Ag⁺ reacts with compounds, or any downstream bioactive effects of transformed AgNPs. Analytical high-resolution transmission electron microscopy has been employed to elucidate cellular uptake and reactivity of AgNWs inside human alveolar epithelial type 1-like cells. AgNWs were observed in the cytoplasm and membrane-bound vesicles, and precipitation of Ag₂S within the cell occurred after 1 h exposure. Cell viability studies showed no evidence of cytotoxicity and reactive oxygen species were not observed on exposure of cells to AgNWs. We suggest that Ag₂S formation acts as a ‘trap’ for free Ag⁺, significantly limiting short-term toxicological effects – with important consequences for the safety of Ag-nanomaterials to human health.

There is a need for novel strategies to treat aggressive breast cancer subtypes and overcome drug resistance. ZnO nanoparticles (NPs) have potential in cancer therapy due to their ability to potently and selectively induce cancer cell apoptosis. Here, we tested the in vitro chemotherapeutic efficacy of ZnONPs loaded via a mesoporous silica nanolayer (MSN) towards drug-sensitive breast cancer cells (MCF-7: estrogen receptor-positive, CAL51: triple-negative) and their drug-resistant counterparts (MCF-7TX, CALDOX). ZnO-MSNs were coated on to gold nanostars (AuNSs) for future imaging capabilities in the NIR-II range. Electron and confocal microscopy showed that MSN–ZnO–AuNSs accumulated close to the plasma membrane and were internalized by cells. High-resolution electron microscopy showed that MSN coating degraded outside the cells, releasing ZnONPs that interacted with cell membranes. MSN–ZnO–AuNSs efficiently reduced the viability of all cell lines, and CAL51/CALDOX cells were more susceptible than MCF7/MCF-7-TX cells. MSN–ZnO–AuNSs were then conjugated with the antibody to Frizzled-7 (FZD-7), the receptor upregulated by several breast cancer cells. We used the disulphide (S–S) linker that could be cleaved with a high concentration of glutathione normally observed within cancer cells, releasing Zn²⁺ into the cytoplasm. FZD-7 targeting resulted in approximately three-fold amplified toxicity of MSN–ZnO–AuNSs towards the MCF-7TX drug-resistant cell line with the highest FZD-7 expression. This study shows that ZnO-MSs are promising tools to treat triple-negative and drug-resistant breast cancers and highlights the potential clinical utility of FZD-7 for delivery of nanomedicines and imaging probes specifically to these cancer types.

ZnO nanoparticles (NPs) are reported to show a high degree of cancer cell selectivity with potential use in cancer imaging and therapy. Questions remain about the mode by which the ZnO NPs cause cell death, whether they exert an intra‐ or extracellular effect, and the resistance among different cancer cell types to ZnO NP exposure. The present study quantifies the variability between the cellular toxicity, dynamics of cellular uptake, and dissolution of bare and RGD (Arg‐Gly‐Asp)‐targeted ZnO NPs by MDA‐MB‐231 cells. Compared to bare ZnO NPs, RGD‐targeting of the ZnO NPs to integrin αvβ3 receptors expressed on MDA‐MB‐231 cells appears to increase the toxicity of the ZnO NPs to breast cancer cells at lower doses. Confocal microscopy of live MDA‐MB‐231 cells confirms uptake of both classes of ZnO NPs with a commensurate rise in intracellular Zn²⁺ concentration prior to cell death. The response of the cells within the population to intracellular Zn²⁺ is highly heterogeneous. In addition, the results emphasize the utility of dynamic and quantitative imaging in understanding cell uptake and processing of targeted therapeutic ZnO NPs at the cellular level by heterogeneous cancer cell populations, which can be crucial for the development of optimized treatment strategies.

Demand for silver engineered nanomaterials (ENMs) is increasing rapidly in optoelectronic and in health and medical applications due to their antibacterial, thermal, electrical conductive, and other properties. The continued commercial up-scaling of ENM production and application needs to be accompanied by an understanding of the occupational health, public safety and environmental implications of these materials. There have been numerous in vitro studies and some in vivo studies of ENM toxicity but their results are frequently inconclusive. Some of the variability between studies has arisen due to a lack of consistency between experimental models, since small differences between test materials can markedly alter their behaviour. In addition, the propensity for the physicochemistry of silver ENMs to alter, sometimes quite radically, depending on the environment they encounter, can profoundly alter their bioreactivity. Consequently, it is important to accurately characterise the materials before use, at the point of exposure and at the nanomaterial-tissue, or “nanobio”, interface, to be able to appreciate their environmental impact. This paper reviews current literature on the pulmonary effects of silver nanomaterials. We focus our review on describing whether, and by which mechanisms, the chemistry and structure of these materials can be linked to their bioreactivity in the respiratory system. In particular, the mechanisms by which the physicochemical properties (e.g., aggregation state, morphology and chemistry) of silver nanomaterials change in various biological milieu (i.e., relevant proteins, lipids and other molecules, and biofluids, such as lung surfactant) and affect subsequent interactions with and within cells will be discussed, in the context not only of what is measured but also of what can be visualized.