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A one-pot method for the synthesis of uniform Eu3+-doped NaBi(MoO4)2 nanoparticles with an ellipsoidal shape and tetragonal crystal structure functionalized with polyacrylic acid is reported for the first time in the literature. The method is based on a homogeneous precipitation reaction from solutions in an ethylene glycol/water medium containing appropriate bismuth, sodium, and molybdate precursors and polyacrylic acid. The luminescence properties (excitation and emission spectra and luminescence lifetime) of such nanoparticles are evaluated for different Eu3+ doping levels, finding an intense red emission for all synthesized samples. The X-ray attenuation properties of the nanoparticles have been also analyzed, which were found to be better than those of a commercially computed tomography contrast agent (iohexol). The dispersibility of the nanoparticles in a physiological medium was also analyzed, finding that they could be well dispersed in a 2-N-morpholinoethanesulfonic acid monohydrate medium (pH = 6.5). Finally, the cell viability of such a phosphor has been analyzed using MIA-PaCa-2 cells and its in vivo toxicity has been evaluated using the nematode Caenorhabditis elegans model finding no significant toxicity in both cases up to a nanoparticle concentration of 100 μg mL−1, which is within the range required for most in vivo applications. The developed Eu3+-doped NaBi(MoO4)2 nanoparticles are, therefore, excellent candidates for their use as bimodal probes for luminescence imaging and X-ray computed tomography.

The combination drug regimens that have long been used to treat tuberculosis (TB), caused by Mycobacterium tuberculosis, are fraught with problems such as frequent administration, long duration of treatment, and harsh adverse effects, leading to the emergence of multidrug resistance. Moreover, there is no effective preventive vaccine against TB infection. In this context, nanoparticles (NPs) have emerged as a potential alternative method for drug delivery. Encapsulating antibiotics in biodegradable NPs has been shown to provide effective therapy and reduced toxicity against M. tuberculosis in different mammalian models, when compared to conventional free drug administration. Here, we evaluate the localization, therapeutic efficacy and toxic effects of polymeric micellar NPs encapsulating a promising but highly hydrophobic and toxic antitubercular drug bedaquiline (BQ) in zebrafish embryos infected with Mycobacterium marinum. Our study shows that the NP formulation of BQ improves survival and reduces bacterial burden in the infected embryos after treatment when compared to its free form. The intravenously injected BQ NPs have short circulation times due to their rapid and efficient uptake into the endothelial cells, as observed by correlative light and electron microscopy (CLEM).

In this work, we report the use of bioorthogonal chemistry, specifically the strain-promoted click azide–alkyne cycloaddition (SPAAC) for the covalent attachment of magnetic nanoparticles (MNPs) on living cell membranes. Four types of MNPs were prepared, functionalized with two different stabilizing/passivation agents (a polyethylene glycol derivative and a glucopyranoside derivative, respectively) and two types of strained alkynes with different reactivities: a cyclooctyne (CO) derivative and a dibenzocyclooctyne (DBCO) derivative. The MNPs were extensively characterized in terms of physicochemical characteristics, colloidal stability, and click reactivity in suspension. Then, the reactivity of the MNPs toward azide-modified surfaces was evaluated as a closer approach to their final application in a living cell scenario. Finally, the DBCO-modified MNPs, showing superior reactivity in suspension and on surfaces, were selected for cell membrane immobilization via the SPAAC reaction on the membranes of cells engineered to express azide artificial reporters. Overall, our work provides useful insights into the appropriate surface engineering of nanoparticles to ensure a high performance in terms of bioorthogonal reactivity for biological applications., This work has been supported by the European Commission, MagicCellGene Project (M-ERA.NET COFUND call 2016, funded by Ministerio de Economía y Competitividad, MINECO, Spain in the framework of the PCIN-2017-060 project), Ministerio de Innovación, Ciencia y Universidades (MCIU, PGC2018-096016-B-I00 to R.M.F), Ministerio de Economía, Industria y Competitividad (BIO 2017-84246-C2-1R to V.G. and J.M.F.), and MINECO and FSE/Agencia Estatal de Investigación (Ramón y Cajal subprogram, grant RYC-2015-17640 to R.M.F.). J.I.L. and E.M.A acknowledge financial support for their predoctoral fellowships from Gobierno de Aragón (DGA 2017–2021 call, co-funded by the Programa Operativo Fondo Social Europeo de Aragón 2014–2020) and Ministerio de Universidades (FPU17/02024), respectively. Authors also acknowledge support from Gobierno de Aragón and Fondos Feder for funding the Bionanosurf (E15_20R) research group. J.M.A. and M.E. acknowledge support from the Basque Government (GIC-2015_IT-1033-16).

Bioorthogonal chemistry comprises chemical reactions that can take place inside complex biological environments, providing outstanding tools for the investigation and elucidation of biological processes. Its use in combination with nanotechnology can lead to further developments in diverse areas of biomedicine, such as molecular bioimaging, targeted delivery, in situ drug activation, study of cell–nanomaterial interactions, biosensing, etc. Here, we summarise the recent efforts to bring together the unique properties of nanoparticles and the remarkable features of bioorthogonal reactions to create a toolbox of new or improved biomedical applications. We show how, by joining forces, bioorthogonal chemistry and nanotechnology can overcome some of the key current limitations in the field of nanomedicine, providing better, faster and more sensitive nanoparticle-based bioimaging and biosensing techniques, as well as therapeutic nanoplatforms with superior efficacy., This work has been supported by the European Commission, MagicCellGene Project (M-ERA.NET COFUND call 2016, funded by Ministerio de Economía y Competitividad, MINECO, Spain in the framework of the PCIN-2017-060 project), Ministerio de Innovación, Ciencia y Universidades (MCIU, PGC2018-096016-B-I00 to R. M. F.), Ministerio de Economía, Industria y Competitividad (BIO 2017-84246-C2-1R to J. M. F.) and MINECO and FSE/Agencia Estatal de Investigación (Ramón y Cajal subprogram, grant RYC-2015-17640 to R.M.F.). R. M. F. also acknowledges financial support from European Union's Horizon 2020 research and innovation programme under the MarieSkłodowska-Curie grant agreement No. 657215. J. I. L. and E. M. A. acknowledge financial support for their predoctoral fellowships from Gobierno de Aragón (DGA 2017-2021 call, co-funded by the Programa Operativo Fondo Social Europeo de Aragón 2014-2020) and Ministerio de Universidades (FPU17/02024), respectively. Authors also acknowledge support from Gobierno de Aragón and Fondos Feder for funding the Bionanosurf (E15_17R) research group. For the table of content figure the authors would like to acknowledge help from Miguel Ruiz and the use of resources from Servier Medical Art (https://smart.servier.com) and Flaticon (https://www.flaticon.com). Part of Figure 14 was created with BioRender.com.

Developing artificial metalloenzymes that possess a superior performance to their natural counterparts is an attractive concept. Polyoxometalates (POMs) are a class of anionic molecular metal–oxides with excellent redox properties and bioactivity. We have recently introduced “POMlymers” – covalently conjugated POM–peptide hybrid materials – where the polypeptide chain is obtained through a ring-opening polymerisation (ROP) of α-amino acid N-carboxyanhydrides (NCA) on an inorganic POM scaffold. Attracted by the idea of preparing artificial metalloenzymes, here we report the supramolecular self-assembly of POMlymer hybrids into nanoparticles where an optimal environment for catalysis is created. Our results demonstrate that the self-assembly of covalent POMlymers, enhances the peroxidase-like activity of the parent POM anion whereas, in contrast, the catalytic activity for nanoparticles obtained by ionic self-assembly of the same peptide and POM components practically disappears. Furthermore, POMlymer nanoparticles also present antimicrobial and antibiofilm activity against the skin bacterium Staphylococcus epidermidis; whereas, ionic POM–peptide hybrids significantly increase biofilm production and endogenous production of reactive oxygen species. In summary, we present the self-assembly of POMlymer hybrids into nanoparticles and a combination of peroxidase activity and microbiology assays that show that the POM–peptide covalent bond is essential for the stability of the self-assembled nanoparticles and therefore for their catalytic and biological activity., This work was funded through the grant PID2019-109333RB-I00 funded by MCIN/AEI/10.13039/501100011033 (Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación, Spain), through project LINKA20270 i-Link+ 2019 funded by CSIC and through Fondo Social de la DGA (grupo DGA E15_20R). HSC is grateful for a predoctoral fellowship FPU2016/02456 funded by Ministerio de Universidades (Spain). E. A. B. and S. G. M. acknowledge funding from the European Union's Horizon 2020 research and innovation program (Marie Skłodowska-Curie grant agreement no. 845427).

Magnetic hyperthermia is a cancer treatment based on the exposure of magnetic nanoparticles to an alternating magnetic field in order to generate local heat. In this work, 3D cell culture models were prepared to observe the effect that a different number of internalized particles had on the mechanisms of cell death triggered upon the magnetic hyperthermia treatment. Macrophages were selected by their high capacity to uptake nanoparticles. Intracellular nanoparticle concentrations up to 7.5 pg Fe/cell were measured both by elemental analysis and magnetic characterization techniques. Cell viability after the magnetic hyperthermia treatment was decreased to

The combination of different bioimaging techniques, mainly in the field of oncology, allows circumventing the defects associated with the individual imaging modalities, thus providing a more reliable diagnosis. The development of multimodal endogenous probes that are simultaneously suitable for various imaging modalities, such as magnetic resonance imaging (MRI), X-ray computed tomography (CT) and luminescent imaging (LI) is, therefore, highly recommended. Such probes should operate in the conditions imposed by the newest imaging equipment, such as MRI operating at high magnetic fields and dual-energy CT. They should show, as well, high photoluminescence emission intensity for their use in optical imaging and present good biocompatibility. In this context, we have designed a single nanoprobe, based on a core-shell architecture, composed of a luminescent Eu:BaLuF core surrounded by an external HoF shell that confers the probe with very high magnetic transverse relaxivity at high field. An intermediate, optically inert BaLuF layer was interposed between the core and the shell to hinder Eu–Ho cross-relaxation and avoid luminescence quenching. The presence of Ba and Lu, with different K-edges, allows for good X-ray attenuation at high and low voltages. The core-shell nanoparticles synthesized are good potential candidates as trimodal bioprobes for MRI at high field, dual-energy CT and luminescent imaging., This research was funded by the Spanish Ministry of Science, Innovation, and Universities (RTI2018-094426-B-I00). Siemens Healthcare S.L.U. also supported part of the research. We also acknowledge the use of the CNA’s ICTS NanoCT facilities and support from DGA and Fondos Feder for funding Bionanosurf (E15_17R) research group. S. Garcia-Embid acknowledges the Ministerio de Educación, Cultura y Deportes of Spanish Government for a FPU grant (FPU15/04482).

Highlights MnO2@Ce6 nanoprobes-loaded-iPS cells (iPS-MnO2@Ce6) were developed for enhanced photodynamic and immunotherapy against cancer. Under the guidance of multi-mode real-time imaging, iPS-MnO2@Ce6 achieved an enhanced photodynamic therapeutic effect and stimulated a strong anti-tumor immune response in the tumor-bearing mouse. Abstract How to trigger strong anti-tumor immune responses has become a focus for tumor therapy. Here, we report the human-induced pluripotent stem cells (iPSs) to deliver MnO2@Ce6 nanoprobes into tumors for simultaneous photodynamic therapy (PDT) and enhanced immunotherapy. Ce6 photosensitizer was attached on manganese dioxide (MnO2) nanoparticles, and resultant MnO2@Ce6 nanoprobes were delivered into mitomycin-treated iPSs to form iPS-MnO2@Ce6 nanoprobes. The iPS-MnO2@Ce6 actively targeted in vivo tumors, the acidic microenvironment triggered interaction between MnO2 and H2O2, released large quantities of oxygen, alleviated hypoxia in tumor. Upon PDT, singlet oxygen formed, broken iPSs released tumor-shared antigens, which evoked an intensive innate and adaptive immune response against the tumor, improving dendritic cells matured, effector T cells, and natural killer cells were activated. Meanwhile, regulatory T cells were reduced, and then the immune response induced by iPS-MnO2@Ce6 was markedly stronger than the immune reaction induced by MnO2@Ce6 (P

Despite numerous reports on nucleated supramolecular polymerization, the molecular origin of the properties of these supramolecular polymers remains overlooked. Here, the formation of fibers formed by self-assembly of N,N′,N′′-tris(alkoxybenzyl)benzene-1,3,5-tricarboxamides (benzyl-BTAs) has been studied using both simulations and experimental techniques. The simulations show that the fibers exhibit a dynamic behavior with stacking defects that appear and propagate differently depending on the BTA molecular structure. To validate theoretical results, a library of eight benzyl-BTAs has been synthesized to compare their supramolecular polymerizations both in the bulk and in apolar solvents. We show that the molecular organization of monomers and dynamics of supramolecular polymers strongly depend on the number and position of the alkoxy substituents on peripheral phenyl rings. By combining theoretical results with experimental measurements, we elucidate the likely role of competitive hydrogen bonding between the central amides and peripheral ether moieties on the stacking behavior of BTAs and the dynamics of structural defects in supramolecular polymers. Our findings open up new design rules for these dynamic materials., MFJM and ARAP thank E.W. (Bert) Meijer for stimulating discussions, Elisabeth Weyandt for providing several aldehyde starting materials, and acknowledge financial support from NWO (TOP-PUNT Grant 10018944) and the Dutch Ministry of Education, Culture and Science (Gravitation program 024.001.035). RMR, HSC, JB and JMF acknowledge the Ministerio de Ciencia Innovación y Universidades (Spain) for funding through the Ramón y Cajal Program (RYC-2013-12570) and Proyectos I+D+i (CTQ2015-66869-P). HSC is grateful for a FPU fellowship from Ministerio de Educación Cultura y Deporte (Spain). The collaboration between Eindhoven and Mons is supported by the Fonds de la Recherche Scientifique – FNRS and the Fonds Wetenschappelijk Onderzoek under EOS Project No. 30650939. Computational resources have been provided by the Consortium des Équipements de Calcul Intensif (CÉCI), funded by the Fonds de la Recherche Scientifique de Belgique (F.R.S.-FNRS) under Grant No. 2.5020.11 and by the Wallonia Region.

Tumor-derived extracellular vesicles have emerged as an alternative source of cancer biomarkers in liquid biopsies. Despite their clinical potential, traditional methods for isolation and analysis have hampered their translation into the clinic. The use of nanomaterial-based biosensors can speed up the development of analytical methods for quantifying extracellular vesicles in a specific, highly reproducible, robust, fast and inexpensive way. Here we review the utility of extracellular vesicles as a novel type of liquid biopsies and the recent advances in nanoparticle-based biosensors for their analysis. We aim to emphasise the limitations and challenges that hinder extracellular vesicle analysis using these biosensors and point out potential solutions., This work was supported by the TRANSCAN2-JTC2016 call (Project PROSCANEXO), Spanish AEI funds (BIO2017-84246-C2-1-R project and Juan de la Cierva fellowship (IJCI-2016-30520) to M. M.) and Fondo Social de la DGA (grupos DGA). B. M. G. thanks the DGA Fellowship program for her PhD position. The Research Council of Norway, the Norwegian Cancer Society, and the South-Eastern Norway Regional Health Authority are also acknowledged., We acknowledge support of the publication fee by the CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI).

[Objective]: Although great progress has been made in the field of siRNA gene therapy, safe, efficient, and targeted delivery of siRNA are still major challenges in siRNA therapeutics., [Methods]: We developed an up-conversion nanoparticle-based nanocage system. This system protected the siRNA from being degraded by nucleases in organisms and selectively delivered the siRNAs to the tumor sites, due to modifications of targeted molecules on the surfaces of nanocages and local inhalation., [Results]: The siRNAs delivered by the up-conversion nanoparticle nanocages were protected from degradation in transit to the tumor sites, where they accumulated. Compared with the passive target and control groups, the up-conversion nanoparticles based on the nanocage system showed a tumor suppressive effect after approximately 3 weeks of treatment., [Conclusions]: The up-conversion nanoparticle nanocages efficiently delivered vascular endothelial growth factor siRNAs to tumor sites. Mice with lung tumors treated with tumors targeting up-conversion nanoparticle nanocages showed steady body weight changes, high tumor inhibition ratios, and longer survival times., This work is supported by the National Key Basic Research Program (973 Project) (Grant Nos. 2015CB931802 and 2017FYA0205301), the Special Fund for Science and Technology Innovation of Shanghai Jiao Tong University (Grant Nos. YG2017MS70, YG2015MS62, and AF0300179), the Shanghai Municipal Bureau of Economy and Information Technology (Grant No. XC-ZXSJ-02-2016-05), the National Natural Scientific Foundation of China (Grant Nos. 8202010801, 81921002, 81225010, 81028009, and 31170961), the 863 Project of China (Grant No. 2014AA020700), and the Shanghai Science and Technology Fund (Grant No. 13NM1401500).

In the last few years, persistent phosphors with a garnet crystal structure have attracted a great deal of interest for a plethora of applications ranging from bioimaging to anti-counterfeiting technologies. However, the development of synthesis methods to fabricate uniform garnet-based micro and nanoparticles, that are needed for such applications, is not mature at all. This study reports the synthesis of highly uniform yttrium aluminum gallium garnet nanospheres. The method is based on homogeneous precipitation in a polyol medium followed by silica coating and calcination. The nanoparticles resulting after silica removal were also uniform and were easily functionalized with polyacrylic acid. The colloidal stability of the latter in physiological media and their biocompatibility were analyzed. The luminescence of the particles, doped with Ce3+, Cr3+, and Nd3+, was studied by recording emission and excitation spectra and persistent luminescence decay curves. Due to their uniform morphology, high colloidal stability, absence of toxicity, and persistent emission in the visible and near-infrared regions, the reported nanospheres show great potential as persistent luminescent bioimaging probes. In addition, the synthesis method paves the way for future use of this persistent material in other applications that require the phosphor to be in the form of highly uniform nanoparticles., This publication is part of the I +D+I Grants RTI2018-094426-B-I00 and PID2020-118485RB-I00 funded by MCIN/AEI/10.13039/501100011033, by “ERDF A way of making Europe”, and the Fondo Social de la DGA (grupos DGA). Financial support was also provided by Junta de Andalucía (P20_00182). Grants FPU19/00527 and FPU19/01311 were funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future”. This research work was performed in the framework of the Nanomedicine CSIC HUB (Ref. 202180E048).

A fast and environmentally-friendly methodology has been developed by in situ synthesis of gold nanoparticles (AuNPs) on thermosensitive liposomes in different phase-states, obtaining nanohybrids with controllable and tunable plasmon modes within the visible/near-infrared region. Lipid phase, charge and synthesis temperature influence the final arrangement of AuNPs, so when the synthesis is performed on zwitterionic liposomes in fluid phase, discrete AuNPs with plasmon peaks in the visible region are obtained, while in gel phase AuNPs tend to aggregate forming nanoclusters, leading to plasmon bands gradually shifted to the infrared as the synthesis temperature decreases. The formed nanohybrids retain the physical properties of the liposomes (fluidity, degree of hydration, cooperativity) by maintaining the transition temperature in the mild-hyperthermia range, while preserving their light-to-heat conversion properties. Therefore, these nanohybrids can be considered excellent candidates as versatile photothermal agents with controlled drug delivery capacity, being powerful tools for light-mediated therapies., This work was funded by the Spanish MINECO (MAT-2017-86805-R to C.R.M and PID2020-118485-RB-I00 to J.M.F), DGA and Fondos Feder (Bionanosurf E15_17R to J.M.F) and CIBER-Consorcio Centro de Investigación Biomédica en Red (CB16/01/00263 to J.M.F and C.C.A), Instituto de Salud Carlos III (Spanish Ministry of Science and Innovation and European Commision, European Regional Development Fund). DLS and FE-SEM equipment acquisition funded by Generalitat Valenciana—Conselleria d'Educació Investigació Cultura i Esport and EUFEDER “Una forma de hacer Europa” (GVA-IDIFEDER 2018/020).

Although great progress has been made in the field of siRNA gene therapy, safe, efficient, and targeted delivery of siRNA are still major challenges in siRNA therapeutics.We developed an up-conversion nanoparticle-based nanocage system. This system protected the siRNA from being degraded by nucleases in organisms and selectively delivered the siRNAs to the tumor sites, due to modifications of targeted molecules on the surfaces of nanocages and local inhalation.The siRNAs delivered by the up-conversion nanoparticle nanocages were protected from degradation in transit to the tumor sites, where they accumulated. Compared with the passive target and control groups, the up-conversion nanoparticles based on the nanocage system showed a tumor suppressive effect after approximately 3 weeks of treatment.The up-conversion nanoparticle nanocages efficiently delivered vascular endothelial growth factor siRNAs to tumor sites. Mice with lung tumors treated with tumors targeting up-conversion nanoparticle nanocages showed steady body weight changes, high tumor inhibition ratios, and longer survival times.

The contactless heating capacity of magnetic nanoparticles (MNPs) has been exploited in fields such as hyperthermia cancer therapy, catalysis, and enzymatic thermal regulation. Herein, we propose an advanced technology to generate multiple local temperatures in a single-pot reactor by exploiting the unique nanoheating features of iron oxide MNPs exposed to alternating magnetic fields (AMFs). The heating power of the MNPs depends on their magnetic features but also on the intensity and frequency conditions of the AMF. Using a mixture of diluted colloids of MNPs we were able to generate a multi-hot-spot reactor in which each population of MNPs can be selectively activated by adjusting the AMF conditions. The maximum temperature reached at the surface of each MNP was registered using independent fluorescent thermometers that mimic the molecular link between enzymes and MNPs. This technology paves the path for the implementation of a selective regulation of multienzymatic reactions., This work was funded by the European Commission through the HOTZYMES Project (H2020-FETOPEN-RIA 829162), the Spanish Ministry of Economy and Competitiveness under Grant No. MAT2017-88148-R (AEI/FEDER, UE) and the PIE-201960E062 project, AEI (BIO2017-84246-C2-1-R project to V.G. and J.M.F., and PID2019-109514RJ-100 to D.S.), Nanotechnology in translational hyperthermia (HIPERNANO) - RED2018-102626-T, and Fondo Social de la DGA (grupos DGA).

This article belongs to the Special Issue State-of-the-Art Polymer Science and Technology in Spain (2020,2021)., Photoembossing is a powerful photolithographic technique to prepare surface relief structures relying on polymerization-induced diffusion in a solventless development step. Conveniently, surface patterns are formed by two or more interfering laser beams without the need for a lithographic mask. The use of nanosecond pulsed light-based interference lithography strengthens the pattern resolution through the absence of vibrational line pattern distortions. Typically, a conventional photoembossing protocol consists of an exposure step at room temperature that is followed by a thermal development step at high temperature. In this work, we explore the possibility to perform the pulsed holographic exposure directly at the development temperature. The surface relief structures generated using this modified photoembossing protocol are compared with those generated using the conventional one. Importantly, the enhancement of surface relief height has been observed by exposing the samples directly at the development temperature, reaching approximately double relief heights when compared to samples obtained using the conventional protocol. Advantageously, the light dose needed to reach the optimum height and the amount of photoinitiator can be substantially reduced in this modified protocol, demonstrating it to be a more efficient process for surface relief generation in photopolymers. Kidney epithelial cell alignment studies on substrates with relief-height optimized structures generated using the two described protocols demonstrate improved cell alignment in samples generated with exposure directly at the development temperature, highlighting the relevance of the height enhancement reached by this method. Although cell alignment is well-known to be enhanced by increasing the relief height of the polymeric grating, our work demonstrates nano-second laser interference photoembossing as a powerful tool to easily prepare polymeric gratings with tunable topography in the range of interest for fundamental cell alignment studies., Funding has been received from Spanish MICINN project BIO2017-84246-C2-1-R, Gobierno de Aragón and FEDER (EU). SGL was funded by Spanish MINECO fellowship (DI-17-09585).

The gastrointestinal contents of twelve individuals from six odontocete species that stranded between 2018 and 2019 in the Macaronesian Region (Eastern North Atlantic) were examined for the presence of marine debris. In addition, concentrations of eleven organic persistent contaminants (nonylphenols, bisphenols, phthalates and pesticides) were analysed in muscle samples by liquid chromatography. No particles larger than 5 mm were found, except for two plastic labels that were found on the same dolphin. On the contrary, all animals contained microplastics of diverse sizes, most of them being fibres (98.06%, n = 708). The predominant detected pollutants were bisphenols (4–984 ng/g) and DEHP (102–1533 ng/g). Also, except for two individuals, all animals had pesticide levels in their tissues. This work has allowed the establishment of a protocol for the study of microplastic ingestion in cetaceans, and tests the potential of microRaman to improve the understanding of microplastic alteration processes.

A one-pot simple procedure for the synthesis of uniform, ellipsoidal Eu3+-doped sodium lanthanum tungstate and molybdate (NaLa(XO4)2, X = W, Mo) nanophosphors, functionalized with carboxylate groups, is described. The method is based on a homogeneous precipitation process at 120 °C from appropriate Na+, Ln3+ and tungstate or molybdate precursors dissolved in ethylene glycol/water mixtures containing polyacrylic acid. A comparative study of the luminescent properties of both luminescent materials as a function of the Eu3+ doping level has been performed to find the optimum nanophosphor, whose efficiency as X-ray computed tomography contrast agent is also evaluated and compared with that of a commercial probe. Finally, the cell viability and colloidal stability in physiological pH medium of the optimum samples have also been studied to assess their suitability for biomedical applications., This work has been supported by the Spanish Ministry of Science, Innovation and Universities, Spain (RTI2018-094426-B-I00), the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (NANOPHOM, grant agreement no. 715832), DGA and Fondos Feder, Aragón, Spain (Bionanosurf E15_17R) and CSIC, Spain (PIC2016FR1). This work was also supported in part by Siemens Healthcare S.L.U., Spain MM thanks MINECO, Spain for Juan de la Cierva Fellowship.

Bi3+ codoping has been proposed in this work with a twofold objective, namely, enhancing the luminescence emission of Eu3+:LaF3 nanoparticles (NPs) and increasing their X-ray attenuation capacity, with the purpose of obtaining a bimodal bioprobe for luminescence bioimaging and X-ray computed tomography. The synthesis method, reported here for the first time for LaF3 particles, allowed obtaining uniform, nonaggregated NPs using a homogeneous precipitation in polyol medium at room temperature in just 2 h. The simplicity of the synthesis method allows the large-scale production of NPs. LaF3 NPs with different Eu3+ contents were first synthesized to find the critical Eu3+ concentration, producing the highest emission intensity. This concentration was subsequently used to fabricate Bi3+–Eu3+-codoped LaF3 NPs using the same method. The emission intensity of the codoped NPs increased in more than one order of magnitude, thanks to the possibility of excitation through the Bi3+ → Eu3+ energy-transfer band. The luminescence properties of the codoped NPs were analyzed in detail to find the mechanism responsible for the emission enhancement. Finally, it was demonstrated that the high atomic number of Bi3+, higher than that of lanthanides, was an added value of the material because it increased its X-ray attenuation capacity. In summary, the LaF3 NPs codoped with Eu3+ and Bi3+ presented in this work are promising candidates as a bimodal bioprobe for luminescence bioimaging and X-ray computed tomography., We gratefully acknowledge T.C. Rojas for help with TEM. This work was supported by CSIC projects (PIC2016FR1 and PIE201460E005), Fondo Social Europeo-Gobierno de Aragoń and by Siemens Healthcare S.L.U. We acknowledge the use of the CNA’s ICTS NanoCT facilities.

Magnetic nanoparticles (MNPs) are promising tools for a wide array of biomedical applications. One of their most outstanding properties is the ability to generate heat when exposed to alternating magnetic fields, usually exploited in magnetic hyperthermia therapy of cancer. In this contribution, we provide a critical review of the use of MNPs and magnetic hyperthermia as drug release and gene expression triggers for cancer therapy. Several strategies for the release of chemotherapeutic drugs from thermo-responsive matrices are discussed, providing representative examples of their application at different levels (from proof of concept to in vivo applications). The potential of magnetic hyperthermia to promote in situ expression of therapeutic genes using vectors that contain heat-responsive promoters is also reviewed in the context of cancer gene therapy., L.G. and R.M.F. acknowledge financial support from the Ramón y Cajal subprogram (RYC-2014-15512 and RYC-2015-17640). E. M-A. acknowledges financial support from the Asociación Española contra el Cáncer (AECC), CSIC (Programa JAE-Intro) and ICMA (Programa de Iniciación a la Investigación). L.B. acknowledges financial support from Santander fellowships. M.M. acknowledges financial support from the Juan de la Cierva subprogram.

The low efficiency of photodynamic therapy (PDT) is caused by tumor hypoxia and the adaptive immune resistance/evasion of tumor cells, while the currently emerging immune checkpoint therapy restores the intrinsic immune capacities but can't directly attack the tumor cells. Methods: Herein we report an integrated nanoplatform that combines PDT with immunotherapy to enhance photodynamic therapeutic effects and simultaneously inhibit tumor cells resistance/evasion. To achieve this, we fabricated Mn@CaCO3/ICG nanoparticles and loaded them with PD-L1-targeting siRNA. Results: Thanks to the protection of CaCO3 on the loaded ICG and the oxygen produced by MnO2, an enhanced photodynamic therapeutic effect in vitro was observed. In vivo experiments demonstrated that the nanoplatform could efficiently deliver the loaded drug to the tumor tissues and significantly improve tumor hypoxia, which further contributes to the therapeutic effect of PDT in vivo. Moreover, the synergistic benefits derived from the siRNA, which silenced the checkpoint gene PD-L1 that mediates the immune resistance/evasion, resulted in a surprising therapeutic effect to rouse the immune system. Conclusions: The combination treatment strategy has great potential to be developed as a new and robust method for enhanced PDT therapy with high efficiency and a powerful antitumor immune response based on PD-L1 blockade.

Gold nanoclusters (AuNCs) have been covalently linked to a FAD-dependent enzyme, choline oxidase (AuNCs@ChOx), with the objective of using the AuNCs fluorescence at 700 nm for monitoring the enzymatic reaction. The linking methodology has been optimized to obtain oriented binding and as a result the structure of the enzyme changes leading to an enhancement of the intrinsic FAD fluorescence of the enzyme (at 525 nm). During the enzymatic reaction with choline, the AuNCs@ChOx fluorescence intensity at both wavelengths (700 nm and 525 nm) changes proportionally to the choline concentration and can be simultaneously monitored. The mechanism of the analytical signal has been studied and a combination of FRET and O2 quenching was found to be responsible for the changes. A mathematical equation is proposed for modelling the signal. The combination of AuNCs@ChOx with acetylcholinesterase permitted the determination of acetylcholine in a concentration range from 1·10−6 to 1·10-5 M and RSD = 4%. This new approach can potentially be applied to any other flavo-enzyme in order to both increase their FAD fluorescence properties and to move the fluorescence measurement to the NIR region. The biosensor is reversible and avoids the use of conventional fluorophores, which are prone to chemical degradation and present worse biocompatibility., This work was supported by the MINECO of Spain (project CTQ2016-76846R) and research funding from DGA (Fondo Social Europeo) (E25_17R).

Magnetic hyperthermia (MH) was used to treat a murine model of pancreatic cancer. This type of cancer is generally characterized by the presence of dense stroma that acts as a barrier for chemotherapeutic treatments. Several alternating magnetic field (AMF) conditions were evaluated using three-dimensional (3D) cell culture models loaded with magnetic nanoparticles (MNPs) to determine which conditions were producing a strong effect on the cell viability. Once the optimal AMF conditions were selected, in vivo experiments were carried out using similar frequency and field amplitude parameters. A marker of the immune response activation, calreticulin (CALR), was evaluated in cells from a xenograft tumor model after the MH treatment. Moreover, the distribution of nanoparticles within the tumor tissue was assessed by histological analysis of tumor sections, observing that the exposure to the alternating magnetic field resulted in the migration of particles toward the inner parts of the tumor. Finally, a relationship between an inadequate body biodistribution of the particles after their intratumoral injection and a significant decrease in the effectiveness of the MH treatment was found. Animals in which most of the particles remained in the tumor area after injection showed higher reductions in the tumor volume growth in comparison with those animals in which part of the particles were found also in the liver and spleen. Therefore, our results point out several factors that should be considered to improve the treatment effectiveness of pancreatic cancer by magnetic hyperthermia., This work was funded by the European Commission through the MagicCellGene Project (M-ERA.NET COFUND call 2016, funded by Ministerio de Economía y Competitividad, MINECO, Spain, in the framework of the PCIN-2017-060 project to V.G.) and the TBMED project (DT-NMBP-02-2018, ID: 814439 to R.M.F.), Spanish MCIU (PGC2018-096016-B-I00 to R.M.F. and L.G., and project BIO2017-84246-C2-1-R to V.G. and J.M.F.), Fondo Social de la DGA (grupos DGA), Fundación Ibercaja-Universidad de Zaragoza (JIUZ-2018-CIE-03 to L.G.), and Universidad de Zaragoza (UZ-2018-CIE-03 to L.G.). L.B. and Y.F.-A. thank the Santander-Universidad Zaragoza Fellowship program for their Ph.D. position. L.G. and R.M.F. acknowledge financial support from the Ramón y Cajal program (RYC-2014-15512 and RYC-2015-17640).

The appearance and rapid spread of drug resistant strains of tuberculosis (TB), one of the deadliest infectious diseases, pose a serious threat to public health and increase the need for shorter, less toxic, and more effective therapies. Developing new drugs is difficult and often associated with side effects, so nanotechnology has emerged as a tool to improve current treatments and to rescue drugs having elevated toxicity or poor solubility. Due to their size and surface chemistry, antimicrobial-loaded nanocarriers are avidly taken up by macrophages, the main cells hosting Mycobacterium tuberculosis. Macrophages are continuously recruited to infected areas, they can transport drugs with them, making passive targeting a good strategy for TB treatment. Active targeting (decorating surface of nanocarriers with ligands specific to receptors displayed by macrophages) further increases local drug concentration, and thus treatment efficacy. Although in in vivo studies, nanocarriers are often administered intravenously in order to avoid inaccurate dosage in animals, translation to humans requires more convenient routes like pulmonary or oral administration. This report highlights the importance and progress of pulmonary administration, passive and active targeting strategies toward bacteria reservoirs to overcome the challenges in TB treatment., This work was supported by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement No. 842652, the Spanish MICINN projects (Grant Nos. BIO2017-84246-C2-1-R, SAF2017-84839-C2-1-R, and CTQ2015-66869-P), and by the Gobierno de Aragón (Diputación General de Aragón–Fondo Social Europeo). R.M.-R. acknowledges MICINN for funding through the Ramón y Cajal Program (Grant No. RYC-2013-12570). H.S.-C. and A.C.M.-P. are grateful for FPU predoctoral contracts from Ministerio de Educación Cultura y Deporte (Spain) and M.A. is grateful for a predoctoral contract from Gobierno de Aragón (Diputación General de Aragón–Fondo Social Europeo).

Exposure of nanomaterials (NMs) to biological medium results in their direct interaction with biomolecules and the formation of a dynamic biomolecular layer known as the biomolecular corona. Despite numerous published data on nano-biointeractions, the role of protein glycosylation in the formation, characteristics, and fate of such nano-biocomplexes has been almost completely neglected, although most serum proteins are glycosylated. This study aimed to systematically investigate the differences in interaction of metallic NPs with glycosylated vs nonglycosylated transferrin. To reach this aim, we compared interaction mechanisms between differently sized, shaped, and surface-functionalized silver NMs and gold NMs to commercially available human transferrin (TRF), a glycosylated protein, and to its nonglycosylated recombinant form (ngTRF). Bovine serum albumin (BSA) was also included in the study for comparative purposes. Characterization of NMs was performed using transmission electron microscopy and dynamic and electrophoretic light scattering techniques. Fluorescence quenching and circular dichroism methods were used to evaluate protein binding constants on the nanosurface and conformational changes after the protein–NM interactions, respectively. Competitive binding of TRF, ngTRF, and BSA to the surface of different NMs was evaluated by separating them after extraction from protein corona by gel electrophoresis following quantification with a commercial protein assay. The results showed that the binding strength between NMs and transferrin and the changes in the secondary protein structure largely depend not only on NM physicochemical properties but also on the protein glycosylation status. Data gained by this study highlight the relevance of protein glycosylation for all future design, development, and efficacy and safety assessment of NMs., This study is based upon collaborative work from COST Action CA 17140 “Cancer Nanomedicine from the Bench to the Bedside” supported by COST (European Cooperation in Science and Technology). It was financially supported by the “Research Cooperability” Program of the Croatian Science Foundation funded by the European Union from the European Social Fund under the Operational Programme Efficient Human Resources 2014–2020 (grant HRZZ-PZS-2019-02-4323), Ministerio de Ciencia e Innovacion (Spain, grant BIO2017–84246-C2–1-R), Fondo Social de la DGA (grupos DGA), and Croatian Science Foundation (grant number HRZZ-IP-2016-06-2436). The authors would like to acknowledge the use of the Advanced Microscopy Laboratory (INMA-Universidad de Zaragoza) for access to their instrumentation and expertise.

[Background]: Gene and chemical therapy has become one of the rising stars in the field of molecular medicine during the last two decades. However, there are still numerous challenges in the development of efficient, targeted, and safe delivery systems that can avoid siRNA degradation and reduce the toxicity and adverse effects of chemotherapy medicine., [Results]: In this paper, a highly efficient AS1411 aptamer modified, dsDNA and MMP-2 cleavable peptide-fabricated gold nanocage vehicle, which could load doxorubicin hydrochloride (DOX) and siRNAs to achieve a combination of tumor responsive genetic therapy, chemotherapy, and photothermal treatment is presented. Our results show that this combined treatment achieved targeted gene silencing and tumor inhibition. After nearly one month of treatment with DOX-loaded Au-siRNA-PAA-AS1411 nanoparticles with one dose every three days in mice, a synergistic effect promoting the eradication of long-lived tumors was observed along with an increased survival rate of mice. The combined genetic, chemotherapeutic, and photothermal treatment group exhibited more than 90% tumor inhibition ratio (tumor signal) and a ~ 67% survival rate compared with a 30% tumor inhibition ratio and a 0% survival rate in the passive genetic treatment group., [Conclusions]: The development of nanocarriers with double-stranded DNA and MMP-2 cleavable peptides provides a new strategy for the combined delivery of gene and chemotherapy medicine. Au-siRNA-PAA-AS1411 exerts high anticancer activities on lung cancer, indicating immense potentials for clinical application., This work is supported by the Special fund for science and technology innovation of Shanghai Jiao Tong University (YG2017MS70, YG2015MS62, AF0300179 ), National Key Basic Research Program (973 Project) (No.2015CB931802), National Key Research and Development Program of China (2017FYA0205301), Shanghai Municipal Bureau of Economy and Information Technology (XC-ZXSJ-02-2016-05), the National Natural Scientific Foundation of China (Grant Nos. 81225010, 81028009 and 31170961), the 863 project of China (Project No. 2014AA020700) and the Shanghai Science and Technology Fund (13NM1401500).

In this study, we report the synthesis of gold-coated iron oxide nanoparticles capped with polyvinylpyrrolidone (Fe@Au NPs). The as-synthesized nanoparticles (NPs) exhibited good stability in aqueous media and excellent features as contrast agents (CA) for both magnetic resonance imaging (MRI) and X-ray computed tomography (CT). Additionally, due to the presence of the local surface plasmon resonances of gold, the NPs showed exploitable “light-to-heat” conversion ability in the near-infrared (NIR) region, a key attribute for effective photothermal therapies (PTT). In vitro experiments revealed biocompatibility as well as excellent efficiency in killing glioblastoma cells via PTT. The in vivo nontoxicity of the NPs was demonstrated using zebrafish embryos as an intermediate step between cells and rodent models. To warrant that an effective therapeutic dose was achieved inside the tumor, both intratumoral and intravenous routes were screened in rodent models by MRI and CT. The pharmacokinetics and biodistribution confirmed the multimodal imaging CA capabilities of the Fe@AuNPs and revealed constraints of the intravenous route for tumor targeting, dictating intratumoral administration for therapeutic applications. Finally, Fe@Au NPs were successfully used for an in vivo proof of concept of imaging-guided focused PTT against glioblastoma multiforme in a mouse model., Spanish Ministry of Economy, Industry and Competitiveness (CTQ2017-86655-R and BIO2017-84246-C2-1-R), Fondo Social de la DGA (grupos DGA) and by the Regional Ministry of Health of Andalusia (OH-0026-2018)., Associate Laboratory for Green Chemistry—LAQV, Applied Molecular Biosciences Unit –UCIBIO, Portuguese national funds from FCT/MCTES (UIDB/04378/2020 and UIDB/50006/2020)

The biodeterioration of artistic and architectural heritage represents a serious and recurring problem for museums, local authorities, and private collectors alike, where irreparable damage to unique artifacts can result in immeasurable losses to our shared cultural heritage. Here, we present an overview of the current trends in antimicrobial products used to protect heritage items from microbial colonization and prevent their deterioration. From a conservation-restoration standpoint, we contrast and compare traditional antimicrobial products with the state of the art in antimicrobial nanomaterials applied in the heritage conservation field, highlighting the promising potential of various different nanomaterials, as well as points of concern and clear red flags from some of the emerging research. Through an examination of the growing body of research in the academic literature we offer recommendations and practical advice on selecting appropriate microbiological assays and characterization techniques to better evaluate the in vitro and in situ antimicrobial properties of nanomaterials., ASA "This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 840375". SGM acknowledges financial support from Ministerio de Ciencia Innovación y Universidades (Spain) for Proyecto I+D+i PID2019-109333RB-I00, and professional support from the CSIC Interdisciplinary Thematic Platform Open Heritage: Research and Society (PTI-PAIS). IFC acknowledges the Gobierno de Aragón for a doctoral scholarship (2018-2022). LH acknowledges the Consejo Superior de Investigaciones Científicas (CSIC) for a JAE Intro fellowship (JAEINT19_EX_0430)., Marie Sklodowska-Curie grant agreement No 840375: "2D Materials/Polyoxometalate Hybrids for Heritage Conservation HeriCare"

The synthesis of uniform neodymium-doped lanthanum trifluoride nanoparticles with lenticular shape and a mean diameter around 45nm by using a homogeneous precipitation method is reported. The luminescent properties of the synthesized samples in terms of their emission spectra and emission lifetime are analyzed as a function of the Nd content to find the optimum phosphor and its suitability for luminescent imaging in the second biological window. The X-ray attenuation properties of the optimum phosphor are evaluated to investigate their additional ability as contrast agent for X-ray computed tomography. Finally, the colloidal stability of the obtained nanoparticles in physiological medium and their cytotoxicity are also analyzed to assess their aptness for in vivo bioimaging applications., En este trabajo se ha desarrollado un método de síntesis de nanopartículas uniformes de trifluoruro de lantano dopadas con neodimio, con forma lenticular y un diámetro medio en torno a 45nm, basado en un proceso de precipitación homogénea en medio acuoso. Las propiedades luminiscentes de las muestras sintetizadas en términos de sus espectros de emisión y tiempo de vida de las emisiones se han analizado en función del contenido de neodimio (Nd) para determinar el nanofósforo óptimo y su idoneidad para la obtención de imágenes luminiscentes en la segunda ventana biológica. Asimismo, se han evaluado las propiedades de atenuación de rayos X del nanofósforo óptimo para valorar su capacidad adicional como agente de contraste para tomografía computarizada de rayos X. Por último, también se han analizado la estabilidad coloidal de las nanopartículas obtenidas en medio fisiológico y su citotoxicidad para determinar su aplicabilidad para la obtención de imágenes biológicas in vivo.

Adenoviral (Ad) vectors have proven to be important tools for gene and cell therapy, although some issues still need to be addressed, such as undesired interactions with blood components and off-target sequestration that ultimately hamper efficacy. In the past years, several organic and inorganic materials have been developed to reduce immunogenicity and improve biodistribution of Ad vectors. Here we investigated the influence of the functionalization of 14 nm PEGylated gold nanoparticles (AuNPs) with quaternary ammonium groups and an arginine-glycine-aspartic acid (RGD)-motif on the uptake and biodistribution of Ad vectors. We report the formation of Ad@AuNPs complexes that promote cell attachment and uptake, independently of the presence of the coxsackievirus and adenovirus receptor (CAR) and αvβ3 and αvβ5 integrins, significantly improving transduction without limiting Ad bioactivity. Besides, the presence of the RGD peptide favors tumor targeting and decreases Ad sequestration in the liver. Additionally, tumor delivery of a coated Ad vector expressing the human sodium iodide symporter (hNIS) by mesenchymal stem cells induces increased accumulation of radioactive iodine (131I) and tumor volume reduction compared to naked Ad-hNIS, highlighting the promising potential of our coating formulation in cancer gene therapy. Statement of significance: Modification of adenoviral vectors with lipids and polymers can reduce interactions with blood components and increase tumor accumulation; however, increased toxicity and reduced transduction efficiency were indicated. Coating with gold nanoparticles has proven to be a successful strategy for increasing the efficiency of transduction of receptor-defective cell lines. Here we explore the contribution of cell surface receptors on the mechanisms of entry of Ad vectors coated with gold nanoparticles in cell lines with varying degrees of resistance to infection. The enhancement of the anti-tumoral effect shown in this work provides new evidence for the potential of our formulation., This research was supported by Instituto de Salud Carlos III (ISCIII) (PI19/01007) and by Fondo Europeo de Desarrollo Regional (Feder) “Una manera de hacer Europa”. We also thank CIBER-BBN, an initiative funded by the VI National R&D&i Plan 2008–2011 financed by the Instituto de Salud Carlos III (ISCIII) with the assistance of the European Regional Development Fund. This study was also partially funded by the Aragon Government (Ph.D. Grant No.r B054/12) and cofounded by Aragon/FEDER 2014–2020 “Building Europe from Aragon”.

Uniform cobalt ferrite nanoparticles have been synthesized using an electrochemical synthesis method in aqueous media. Their colloidal, magnetic, and relaxometric properties have been analyzed. The novelty of this synthesis relies on the use of iron and cobalt foils as precursors, which assures the reproducibility of the iron and cobalt ratio in the structure. A stable and biocompatible targeting conjugate nanoparticle-folic acid (NP-FA) was developed that was capable of targeting FA receptor positivity in HeLa (human cervical cancer) cancer cells. The biocompatibility of NP-FA was assessed in vitro in HeLa cells using the MTT assay, and morphological analysis of the cytoskeleton was performed. A high level of NP-FA binding to HeLa cells was confirmed through qualitative in vitro targeting studies. A value of 479 Fe+Co mM􀀀1s􀀀1 of transverse relaxivity (r2) was obtained in colloidal suspension. In addition, in vitro analysis in HeLa cells also showed an important effect in negative T2 contrast. Therefore, the results show that NP-FA can be a potential biomaterial for use in bio medical trials, especially as a contrast agent in magnetic resonance imaging (MRI)., We are grateful for the financial support provided by the Spanish Ministry of Economy and Competitiveness who funded this research under project PGC2018-095642-B-I00 and to the Fondo Social Europeo-Gobierno de Aragón, Ministerio de la Economía y Competitividad del Gobierno de España for the public funding of Proyectos I+D+I—Programa Estatal de Investigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad (project n. BIO2017-84246-C2-1-R).

Lipids are a major source of energy for most tissues, and lipid uptake and storage is therefore crucial for energy homeostasis. So far, quantification of lipid uptake in vivo has primarily relied on radioactive isotope labeling, exposing human subjects or experimental animals to ionizing radiation. Here, we describe the quantification of in vivo uptake of chylomicrons, the primary carriers of dietary lipids, in metabolically active tissues using magnetic particle imaging (MPI) and magnetic particle spectroscopy (MPS). We show that loading artificial chylomicrons (ACM) with iron oxide nanoparticles (IONPs) enables rapid and highly sensitive post hoc detection of lipid uptake in situ using MPS. Importantly, by utilizing highly magnetic Zn-doped iron oxide nanoparticles (ZnMNPs), we generated ACM with MPI tracer properties superseding the current gold-standard, Resovist, enabling quantification of lipid uptake from whole-animal scans. We focused on brown adipose tissue (BAT), which dissipates heat and can consume a large part of nutrient lipids, as a model for tightly regulated and inducible lipid uptake. High BAT activity in humans correlates with leanness and improved cardiometabolic health. However, the lack of nonradioactive imaging techniques is an important hurdle for the development of BAT-centered therapies for metabolic diseases such as obesity and type 2 diabetes. Comparison of MPI measurements with iron quantification by inductively coupled plasma mass spectrometry revealed that MPI rivals the performance of this highly sensitive technique. Our results represent radioactivity-free quantification of lipid uptake in metabolically active tissues such as BAT., S.H., L.R.-S., and A.P. thank the DFG (FOR917, 335447717/SFB1328, and 397484323/SFB TRR 259/1) and DAAD (57172123) for funding. Z.N. was supported by the Bonn International Graduate School of Drug Sciences (BIGS DrugS), University of Bonn, and A.P. is member of the PharmaCenter Bonn, University of Bonn, Germany. N.L., H.P., and F.W. would like to acknowledge the Federal Ministry of Economics and Technology within the TransMeT project “Magnetische Messtechnik für die Größenfraktionierung magnetischer Nanopartikel”, the DFG Grant SHA 1506/2-1 “AMPI: Magnetic particle imaging: Development and evaluation of novel methodology for the assessment of the aorta in vivo in a small animal model of aortic aneurysms”, the DFG grant TR 408/9-1 “quantMPI: Establishment of quantitative Magnetic Particle Imaging (MPI) application oriented phantoms for preclinical investigations”, and the DFG grant “Matrix in Vision” (SFB 1340/1 2018, no 372486779, project A02). N.T.K.T. thanks EPSRC (EP/M018016/1 and EP/M015157/1) and AOARD (FA2386-17-1-4042 award) for funding. G.K. would like to acknowledge EPSRC for his Ph.D. studentship. T.T. thanks the Royal Thai Government for his Ph.D. studentship. The microscopy work was conducted in the “Laboratorio de Microscopias Avanzadas” at “Instituto de Nanociencia de Aragón–Universidad de Zaragoza”. The authors acknowledge the LMA-INA for offering access to their instruments and expertise. R.M.F. acknowledges financial support from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 657215 and from Ministerio de Economía y Competitividad (Ramón y Cajal subprogram RYC-2015-17640). J.M.F. also acknowledges financial support from Spanish MINECO (project BIO2017-84246-C2-1-R) and DGA and Fondos Feder (Bionanosurf E15_17R). The authors would like to acknowledge the LA-ICPMS laboratory of the Institute of Geosciences and Meterology, University of Bonn, for performing ICP-MS measurements.

The exploitation of silver nanoparticles (AgNPs) in biomedicine represents more than one third of their overall application. Despite their wide use and significant amount of scientific data on their effects on biological systems, detailed insight into their in vivo fate is still lacking. This study aimed to elucidate the biotransformation patterns of AgNPs following oral administration. Colloidal stability, biochemical transformation, dissolution, and degradation behaviour of different types of AgNPs were evaluated in systems modelled to represent biological environments relevant for oral administration, as well as in cell culture media and tissue compartments obtained from animal models. A multimethod approach was employed by implementing light scattering (dynamic and electrophoretic) techniques, spectroscopy (UV–vis, atomic absorption, nuclear magnetic resonance) and transmission electron microscopy. The obtained results demonstrated that AgNPs may transform very quickly during their journey through different biological conditions. They are able to degrade to an ionic form and again reconstruct to a nanoparticulate form, depending on the biological environment determined by specific body compartments. As suggested for other inorganic nanoparticles by other research groups, AgNPs fail to preserve their specific integrity in in vivo settings., This study was based upon a collaborative work from COST Action CA 17140 "Cancer Nanomedicine from the Bench to the Bedside" supported by COST (European Cooperation in Science and Technology). It was financially supported by the Croatian Science Foundation (grant number HRZZ-IP-2016-06-2436), the Ministerio de Ciencia e Innovacion and Fondo Social Europeo/Agencia Estatal de Investigación (Spain, grant BIO2017-84246-C2-1-R and Ramón y Cajal subprogram, grant RYC-2015-17640), Fondo Social de la DGA (grupos DGA).

The ring-opening polymerisation of α-amino acid N-carboxyanhydrides (NCAs) offers a simple and scalable route to polypeptides with predicted and narrow molecular weight distributions. Here we show how polyoxometalates (POMs)—redox-active molecular metal-oxide anions—can serve as inorganic scaffold initiators for such NCA polymerisations. This “On-POM polymerisation” strategy serves as an innovative platform to design hybrid materials with additive or synergistic properties stemming from the inorganic and polypeptide component parts. We have used this synthetic approach to synthesise a library of bactericidal poly(lysine)–POM hybrid derivatives that can be used to prevent biofilm formation. This versatile “On-POM polymerisation” method provides a flexible synthetic approach for combining inorganic scaffolds with amino acids, and the potential to tailor and improve the specificity and performance of hybrid antimicrobial materials., Financial support from Ministerio de Ciencia Innovación y Universidades (Spain) through a Ramón y Cajal fellowship (RMR, RYC-2013-12570) and Proyectos I+D+i (PID2019-109333RB-I00, PGC2018-097583-B-I00, and PID2019-105881RB-I00) and CSIC i-Link+2019 project (LINK20270). HSC and IFC are grateful for predoctoral fellowships from Ministerio de Educación Cultura y Deporte (FPU program) and Gobierno de Aragón, respectively. Further financial support from Fondo Social Europeo-Gobierno de Aragón (E15_20R, E47_20R and E31_17R) and CIBER-BBN is gratefully acknowledged. The authors would like to acknowledge the Laboratorio de Microscopías Avanzadas (LMA) at Universidad de Zaragoza for offering access to their instruments and expertise, especially Guillermo Antorrena for the XPS measurements; the use of the Unidad de Apoyo a la Investigación del CEQMA (CSIC-Universidad de Zaragoza).