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Nanoparticle-sensitized photoporation is an upcoming approach for intracellular delivery of biologics, combining high efficiency and throughput with excellent cell viability. However, as it relies on close contact between nanoparticles and cells, its translation towards clinical applications is hampered by safety and regulatory concerns. Here, we show that light-sensitive iron oxide nanoparticles (IONPs) embedded in biocompatible electrospun nanofibers induce membrane permeabilization by photothermal effects without direct cellular contact with IONPs. The photothermal nanofibers are successfully used to deliver effector molecules, including CRISPR/Cas9 ribonucleoprotein complexes and siRNA, in adherent and suspension cells, including embryonic stem cells and hard-to-transfect T-cells without affecting cell proliferation or phenotype. In vivo experiments furthermore demonstrate successful tumor regression in mice treated with CAR-T cells in which expression of PD1 is downregulated after nanofiber photoporation with siPD1. In conclusion, cell membrane permeabilization with photothermal nanofibers is a promising concept towards the safe and more efficient production of engineered cells for therapeutic applications, including stem cell or adoptive T cell therapy.

Whales accumulate mercury (Hg), but do not seem to show immediate evidence of toxic effects. Analysis of different tissues (liver, kidney, muscle) and biofluids (blood, milk) from a pod of stranded long-finned pilot whales ( Globicephala melas ) showed accumulation of Hg as a function of age, with a significant decrease in the MeHg fraction. Isotopic analysis revealed remarkable differences between juvenile and adult whales. During the first period of life, Hg in the liver became isotopically lighter (δ 202 Hg decreased) with a strongly decreasing methylmercury (MeHg) fraction. We suggest this is due to preferential demethylation of MeHg with the lighter Hg isotopes and transport of MeHg to less sensitive organs, such as the muscles. Also changes in diet, with high MeHg intake in utero and during lactation, followed by increasing consumption of solid food contribute to this behavior. Interestingly, this trend in δ 202 Hg is reversed for livers of adult whales (increasing δ 202 Hg value), accompanied by a progressive decrease of δ 202 Hg in muscle at older ages. These total Hg (THg) isotopic trends suggest changes in the Hg metabolism of the long-finned pilot whales, development of (a) detoxification mechanism(s) ( e.g ., though the formation of HgSe particles), and Hg redistribution across the different organs.

This work reviews the operating principles of ICP-tandem mass spectrometry (ICP-MS/MS) and the key applications reported on since the introduction of the technique in 2012.

In this work, the effects of using collision/reaction cell (CRC) technology in quadrupole-based ICP-MS 16 (ICP-QMS) instrumentation operated in single-particle (SP) mode have been assessed. The influence 17 of (i) various CRC gases, (ii) gas flow rates, (iii) nanoparticle (NP) sizes and (iv) NP types was evaluated 18 using Ag, Au and Pt NPs with both a traditional ICP-QMS instrument and a tandem ICP-mass 19 spectrometer. It has been shown that using CRC technology brings about a significant increase in the 20 NP signal peak width (from 0.5 up to 6 ms). This effect is more prominent for a heavier gas (e.g., NH 3) 21 than for a lighter one (e.g., H 2 or He). At a higher gas flow rate and/or for larger particle sizes (>100 been further demonstrated by characterizing custom-made 50 and 200 nm Fe 3 O 4 NPs (originally 1 strongly affected by the occurrence of spectral overlap) using different CRC approaches (H 2 on-mass 2 and NH 3 mass-shift). The use of NH 3 (monitoring of Fe as the Fe(NH 3) 2 + reaction product ion at m/z = 3 90 amu) induces a significant peak broadening compared to that observed when using H 2 (6.10 ± 1.60 4 vs. 0.94 ± 0.49 ms). This extension of transit time can most likely be attributed to the 5 collisions/interactions of the ion cloud generated by a single NP event with the CRC gas and it even 6 precludes 50 nm Fe 3 O 4 NPs to be detected when using the NH 3 mass-shift approach. Based on these 7 results, the influence of a longer peak width on the accuracy of SP-ICP-MS measurement data (NP 8 size, particle number density and mass concentration) must be taken into account when using CRC 9 technology as a means to overcome spectral overlap. To mitigate the potential detrimental effect of 10 using CRC technology in the characterization of NPs via SP-ICP-MS(/MS), the use of light gases and 11 low gas flow rates is recommended. 12