A Photodynamic and Photochemotherapeutic Platinum-Iridium Charge-Transfer Conjugate for Anticancer Therapy.

The novel hetero-dinuclear complex trans,trans,trans-[PtIV(py)2(N3)2(OH)(µ-OOCCH2CH2CONHCH2-bpyMe)IrIII(ppy)2]Cl (Pt-Ir), exhibits charge transfer between the acceptor photochemotherapeutic Pt(IV) (Pt-OH) and donor photodynamic Ir(III) (Ir-NH2) fragments. It is stable in the dark, but undergoes photodecomposition more rapidly than the Pt(IV) parent complex (Pt-OH) to generate Pt(II) species, an azidyl radical and 1O2. The Ir(III)* excited state, formed after irradiation, can oxidise NADH to NAD⋅ radicals and NAD+. Pt-Ir is highly photocytotoxic towards cancer cells with a high photocytotoxicity index upon irradiation with blue light (465 nm, 4.8 mW/cm2), even with short light-exposure times (10-60 min). In contrast, the mononuclear Pt-OH and Ir-NH2 subunits and their simple mixture are much less potent. Cellular Pt accumulation was higher for Pt-Ir compared to Pt-OH. Irradiation of Pt-Ir in cancer cells damages nuclei and releases chromosomes. Synchrotron-XRF revealed ca. 4× higher levels of intracellular platinum compared to iridium in Pt-Ir treated cells under dark conditions. Luminescent Pt-Ir distributes over the whole cell and generates ROS and 1O2 within 1 h of irradiation. Iridium localises strongly in small compartments, suggestive of complex cleavage and excretion via recycling vesicles (e.g. lysosomes). The combination of PDT and PACT motifs in one molecule, provides Pt-Ir with a novel strategy for multimodal phototherapy.

Synchrotron XRF and Histological Analyses Identify Damage to Digestive Tract of Uranium NP-Exposed Daphnia magna.

Micro- and nanoscopic X-ray techniques were used to investigate the relationship between uranium (U) tissue distributions and adverse effects to the digestive tract of aquatic model organism Daphnia magna following uranium nanoparticle (UNP) exposure. X-ray absorption computed tomography measurements of intact daphnids exposed to sublethal concentrations of UNPs or a U reference solution (URef) showed adverse morphological changes to the midgut and the hepatic ceca. Histological analyses of exposed organisms revealed a high proportion of abnormal and irregularly shaped intestinal epithelial cells. Disruption of the hepatic ceca and midgut epithelial tissues implied digestive functions and intestinal barriers were compromised. Synchrotron-based micro X-ray fluorescence (XRF) elemental mapping identified U co-localized with morphological changes, with substantial accumulation of U in the lumen as well as in the epithelial tissues. Utilizing high-resolution nano-XRF, 400-1000 nm sized U particulates could be identified throughout the midgut and within hepatic ceca cells, coinciding with tissue damages. The results highlight disruption of intestinal function as an important mode of action of acute U toxicity in D. magna and that midgut epithelial cells as well as the hepatic ceca are key target organs.

Spatially Resolved Dissolution and Speciation Changes of ZnO Nanorods during Short-Term in Situ Incubation in a Simulated Wastewater Environment.

Zinc oxide engineered nanomaterials (ZnO ENMs) are used in a variety of applications worldwide due to their optoelectronic and antibacterial properties with potential contaminant risk to the environment following their disposal. One of the main potential pathways for ZnO nanomaterials to reach the environment is via urban wastewater treatment plants. So far there is no technique that can provide spatiotemporal nanoscale information about the rates and mechanisms by which the individual nanoparticles transform. Fundamental knowledge of how the surface chemistry of individual particles change, and the heterogeneity of transformations within the system, will reveal the critical physicochemical properties determining environmental damage and deactivation. We applied a methodology based on spatially resolved in situ X-ray fluorescence microscopy (XFM), allowing observation of real-time dissolution and morphological and chemical evolution of synthetic template-grown ZnO nanorods (∼725 nm length, ∼140 nm diameter). Core-shell ZnO-ZnS nanostructures were formed rapidly within 1 h, and significant amounts of ZnS species were generated, with a corresponding depletion of ZnO after 3 h. Diffuse nanoparticles of ZnS, Zn3(PO4)2, and Zn adsorbed to Fe-oxyhydroxides were also imaged in some nonsterically impeded regions after 3 h. The formation of diffuse nanoparticles was affected by ongoing ZnO dissolution (quantified by inductively coupled plasma mass spectrometry) and the humic acid content in the simulated sludge. Complementary ex situ X-ray absorption spectroscopy and scanning electron microscopy confirmed a significant decrease in the ZnO contribution over time. Application of time-resolved XFM enables predictions about the rates at which ZnO nanomaterials transform during their first stages of the wastewater treatment process.