Multicore liquid perfluorocarbon-loaded multimodal nanoparticles for stable ultrasound and ¹⁹ F MRI applied to in vivo cell tracking

Ultrasound is the most commonly used clinical imaging modality. However, in applications requiring cell-labeling, the large size and short active lifetime of ultrasound contrast agents limit their longitudinal use. Here, 100 nm radius, clinically applicable, polymeric nanoparticles containing a liquid perfluorocarbon, which enhance ultrasound contrast during repeated ultrasound imaging over the course of at least 48 h, are described. The perfluorocarbon enables monitoring the nanoparticles with quantitative 19 F magnetic resonance imaging, making these particles effective multimodal imaging agents. Unlike typical core–shell perfluorocarbon-based ultrasound contrast agents, these nanoparticles have an atypical fractal internal structure. The nonvaporizing highly hydrophobic perfluorocarbon forms multiple cores within the polymeric matrix and is, surprisingly, hydrated with water, as determined from small-angle neutron scattering and nuclear magnetic resonance spectroscopy. Finally, the nanoparticles are used to image therapeutic dendritic cells with ultrasound in vivo, as well as with 19 F MRI and fluorescence imaging, demonstrating their potential for long-term in vivo multimodal imaging. </p

Data from a survey on the impact of the pandemic on early-stage academics

We would like to share data from a survey run by the Young Academy of Europe (YAE) from June to October 2020, with questions aiming to unravel the situation of early-career researchers (including early stage group leaders) working in Europe, during the COVID-19 pandemic. We were particularly interested in the impact of care activities (related to young children or other family members), and the impact of gender. We include the online survey and collected data, without identifying information. The survey is published in Nature Career Column (July, 2021) ( https://www.nature.com/articles/d41586-021-01952-6)

Factors Influencing the Accumulation of Free Asparagine in Wheat Grain and the Acrylamide Formation in Bread

Asparagine is one of the precursors of acrylamide that can form during bread production. The aim of this work was to determine the effect of genotype, environment, sulfur fertilization, and the interaction of those factors on the asparagine content, technological value of wheat, and acrylamide level in bread. The research material consisted of five wheat cultivars grown in two locations in Poland with nitrogen fertilization of 110 kg ha-1 and sulfur fertilization of 30 kg ha-1. The standard ISO method for analyzing the milling and baking properties of wheat was used. The UHPLC-MS/MS method for analyzing the amino acids and the GC/MS method for acrylamide in bread were implemented. The analysis of variance results indicated that the location influenced the total variance in the measured asparagine content and quality of wheat the most, followed by the cultivar and then by the interaction between the environment and cultivar. Sulfur fertilization had no significant effect on the asparagine content, but slightly lowered the gluten quality and loaf volume of bread. However, sulfur fertilization in connection with the cultivar characterized by low starch damage had a positive effect on lowering the acrylamide in bread. Asparagine content in wheat and acrylamide in bread varies mostly depending on cultivar and environment

Customizing poly(lactic-co-glycolic acid) particles for biomedical applications

\u3cp\u3eNano- and microparticles have increasingly widespread applications in nanomedicine, ranging from drug delivery to imaging. Poly(lactic-co-glycolic acid) (PLGA) particles are the most widely-applied type of particles due to their biocompatibility and biodegradability. Here, we discuss the preparation of PLGA particles, and various modifications to tailor particles for applications in biological systems. We highlight new preparation approaches, including microfluidics and PRINT method, and modifications of PLGA particles resulting in novel or responsive properties, such as Janus or upconversion particles. Finally, we describe how the preparation methods can- and should-be adapted to tailor the properties of particles for the desired biomedical application. Our aim is to enable researchers who work with PLGA particles to better appreciate the effects of the selected preparation procedure on the final properties of the particles and its biological implications. Statement of Significance: Nanoparticles are increasingly important in the field of biomedicine. Particles made of polymers are in the spotlight, due to their biodegradability, biocompatibility, versatility. In this review, we aim to discuss the range of formulation techniques, manipulations, and applications of poly(lactic-co-glycolic acid) (PLGA) particles, to enable a researcher to effectively select or design the optimal particles for their application. We describe the various techniques of PLGA particle synthesis and their impact on possible applications. We focus on recent developments in the field of PLGA particles, and new synthesis techniques that have emerged over the past years. Overall, we show how the chemistry of PLGA particles can be adapted to solve pressing biological needs.\u3c/p\u3

Customizing poly(lactic-co-glycolic acid) particles for biomedical applications

Nano- and microparticles have increasingly widespread applications in nanomedicine, ranging from drug delivery to imaging. Poly(lactic-co-glycolic acid) (PLGA) particles are the most widely-applied type of particles due to their biocompatibility and biodegradability. Here, we discuss the preparation of PLGA particles, and various modifications to tailor particles for applications in biological systems. We highlight new preparation approaches, including microfluidics and PRINT method, and modifications of PLGA particles resulting in novel or responsive properties, such as Janus or upconversion particles. Finally, we describe how the preparation methods can- and should-be adapted to tailor the properties of particles for the desired biomedical application. Our aim is to enable researchers who work with PLGA particles to better appreciate the effects of the selected preparation procedure on the final properties of the particles and its biological implications. Statement of Significance: Nanoparticles are increasingly important in the field of biomedicine. Particles made of polymers are in the spotlight, due to their biodegradability, biocompatibility, versatility. In this review, we aim to discuss the range of formulation techniques, manipulations, and applications of poly(lactic-co-glycolic acid) (PLGA) particles, to enable a researcher to effectively select or design the optimal particles for their application. We describe the various techniques of PLGA particle synthesis and their impact on possible applications. We focus on recent developments in the field of PLGA particles, and new synthesis techniques that have emerged over the past years. Overall, we show how the chemistry of PLGA particles can be adapted to solve pressing biological needs

Correction: Fast, quantitative, murine cardiac 19F MRI/MRS of PFCE-labeled progenitor stem cells and macrophages at 9.4T.

[This corrects the article DOI: 10.1371/journal.pone.0190558.]

Encapsulation of Paramagnetic Chelates in Perfluorocarbon-loaded Fractal Nanoparticles Enables Modulation of Fluorine-19 and Proton Magnetic Resonance Imaging Signal

19F magnetic resonance imaging (19F MRI) is an emerging technique for quantitative imaging of novel therapies, such as cellular therapies and theranostic nanocarriers. A modification of perfluorocarbon (PFC)-loaded, nanocarrier-based 19F MRI probes with paramagnetic chelates can enhance probe’s functionality. Liquid PFC-loaded nanocarriers typically have a core-shell structure with PFC in the core due to the poor miscibility of PFC. However, paramagnetic relaxation enhancement acts only at a distance of a few angstroms. Thus, efficient modulation of 19F signal is possible only with fluorophilic PFC-soluble chelates. Such chelates, however, cannot interact with the surroundings of nanocarriers. Conversely, chelates on the surface typically affect only the aqueous environment but not the 19F signal. We show that the confinement of PFC in biodegradable polymeric nanoparticles with fractal structure enables modulation of longitudinal and transverse 19F relaxation, as well as proton signal, using non-fluorophilic paramagnetic chelates. We compared nanoparticles with fractal multicore versus conventional core-shell structure, where the PFC is encapsulated in the core(s) and the chelate in the surrounding polymeric matrix. Importantly, paramagnetic chelates affected both longitudinal and transverse 19F relaxation in fractal multicore nanoparticles, but not in core-shell nanocapsules. Both relaxation rates of 19F nucleus increased with an increasing concentration of the paramagnetic chelate. Moreover, as the polymeric matrix remained water-permeable, proton enhancement additionally was observed in MRI. In the future, the effects of fractal confinement could be combined with more effective paramagnetic chelates to develop multifunctional imaging probes, for example, for high-sensitivity 19F MRI combined with sensing

CPC label confirmation using flow cytometry and in vitro ¹⁹F MRI/MRS validation.

<p><b>(A, B, D, E)</b> Ungated scatter plots of forward (FSC) and side scatter (SSC, singlets vs. doublets) and <b>(C, F)</b> gated, overlapped flow cytometry histograms of control <b>(C)</b> and labeled CT cells <b>(F)</b> confirming cellular uptake. Applied gates are indicated in the scatter plots as highlighted regions-of-interest. <b>(G, H)</b> Confocal microscopy images of PFCE labelled <b>(G)</b> CDC GFP+ (calcein [gray]), <b>(H)</b> Atto647 (red), and (<b>I)</b> merged calcein/Atto647 with a zoomed inlet indicating the heterogenous distribution of cellular label uptake. <b>(J, K)</b> Corresponding ¹⁹F and ¹H-¹⁹F merged MRI of labeled CT cells (~4.5 million) obtained using the solenoid coil showing excellent ¹⁹F signal localization. <b>(L)</b> ¹⁹F magnitude spectrum in labeled CTs using the solenoid coil (line broadening = 30 Hz, zero reference frequency set to the NP-labeled CT cell resonance).</p