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Temperature monitoring is useful in medical diagnosis, and essential during hyperthermia treatments to avoid undesired cytotoxic effects. Aiming to control heating doses, different temperature monitoring strategies have been developed, largely based on luminescent materials, a.k.a. nanothermometers. However, for such nanothermometers to work, both excitation and emission light beams must travel through tissue, making its optical properties a relevant aspect to be considered during the measurements. In complex tissues, heterogeneity, and real-time alterations as a result of therapeutic treatment may have an effect on light-tissue interaction, hindering accuracy in the thermal reading. In this Tutorial Review we discuss various methods in which nanothermometers can be used for temperature sensing within heterogeneous environments. We discuss recent developments in optical (nano)thermometry, focusing on the incorporation of luminescent nanoparticles into complex in vitro and in vivo models. Methods formulated to avoid thermal misreading are also discussed, considering their respective advantages and drawbacks.

Hyperthermia, as the process of heating a malignant site above 42 °C to trigger cell death, has emerged as an effective and selective cancer therapy strategy. Various modalities of hyperthermia have been proposed, among which magnetic and photothermal hyperthermia are known to benefit from the use of nanomaterials. In this context, we introduce herein a hybrid colloidal nanostructure comprising plasmonic gold nanorods (AuNRs) covered by a silica shell, onto which iron oxide nanoparticles (IONPs) are subsequently grown. The resulting hybrid nanostructures are responsive to both external magnetic fields and near-infrared irradiation. As a result, they can be applied for the targeted magnetic separation of selected cell populations – upon targeting by antibody functionalization – as well as for photothermal heating. Through this combined functionality, the therapeutic effect of photothermal heating can be enhanced. We demonstrate both the fabrication of the hybrid system and its application for targeted photothermal hyperthermia of human glioblastoma cells.

The incidence and mortality of cancer demand more innovative approaches and combination therapies to increase treatment efficacy and decrease off-target side effects. We describe a boron-rich nanoparticle composite with potential applications in both boron neutron capture therapy (BNCT) and photothermal therapy (PTT). Our strategy is based on gold nanorods (AuNRs) stabilized with polyethylene glycol and functionalized with the water-soluble complex cobalt bis(dicarbollide) ([3,3'-Co(1,2-C(2)B9H(11))(2)](-)), commonly known as COSAN. Radiolabeling with the positron emitter copper-64 (Cu-64) enabled in vivo tracking using positron emission tomography imaging. Cu-64-labeled multi-functionalized AuNRs proved to be radiochemically stable and capable of being accumulated in the tumor after intravenous administration in a mouse xenograft model of gastrointestinal cancer. The resulting multifunctional AuNRs showed high biocompatibility and the capacity to induce local heating under external stimulation and trigger cell death in heterogeneous cancer spheroids as well as the capacity to decrease cell viability under neutron irradiation in cancer cells. These results position our nanoconjugates as suitable candidates for combined BNCT/PTT therapies.

The development of optical nanothermometers operating in the near-infrared (NIR) is of high relevance toward temperature measurements in biological systems. We propose herein the use of Nd3+-doped lanthanum oxychloride nanocrystals as an efficient system with intense photoluminescence under NIR irradiation in the first biological transparency window and emission in the second biological window with excellent emission stability over time under 808 nm excitation, regardless of Nd3+ concentration, which can be considered as a particular strength of our system. Additionally, surface passivation through over-growth of an inert LaOCl shell around optically active LaOCl/Nd3+ cores was found to further enhance the photoluminescence intensity and also the lifetime of the 1066 nm, F-4(3/2) to I-4(11/2) transition, without affecting its (ratiometric) sensitivity toward temperature changes. As required for biological applications, we show that the obtained (initially hydrophobic) nanocrystals can be readily transferred into aqueous solvents with high, long-term stability, through either ligand exchange or encapsulation with an amphiphilic polymer. The authors thank the financial support of the European Research Council (ERC-AdG-2017 787510, ERC-CoG-2019 815128) and of the European Commission (EUSMI, Grant 731019). This work was performed under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency-Grant MDM-2017-0720.

Laponite is a nanoplatform that has been successfully used as a new biomaterial for drug delivery, tissue engineering and bioimaging at the nanoscale. In general, a deep knowledge of the mechanism interaction of the nanomaterial with biological components in a physiological environment is highly desirable for properly characterizing its therapeutic efficacy and toxicology. Up to know, the use of fluorescent dyes labelling both, the nanomaterial and cell components, has been a requirement to characterize the cell uptake and to visualize the entrance of the nanomaterial into the cytosol and the cell nucleus. The used of fluorophores usually perturb the physiological medium and can interfere in the nanomaterial cell interaction. A new Raman imaging methodology to track the uptake and internalization of Laponite nanoparticles into J774 macrophages line cells is presented in this work. The combination of Raman spectroscopy and confocal microscopy provides direct information about the localization of the nanoparticle into the cell, through its unique vibrational fingerprint without labelling or adding dyes, and taking advantage of the fact that Laponite and biological molecules bands can be clearly differentiated. We would like to thank IDIVAL for financial support, Projects N°NVAL16/17, INNVAL19/18 and NVAL18/07. CRL thanks the MINECO for the Juan de la Cierva Formación grant (ref. FJCI-2015-25306). This work has been supported by the Spanish MINECO, Instituto de Salud Carlos III, the European Union FEDER funds under Projects ref. PI16/00496 (AES 2016), PI19/00349 and DTS19/00033 (AES 2019). The authors are grateful to Dr F Madrazo and the Laser Microscopy Unit of the IDIVAL Institute for the use of the Confocal Raman Imaging Microscope.

Understanding the biological effects triggered by nanomaterials is crucial, not only in nanomedicine but also in toxicology. The dose-response relation is relevant in biological tests due to its use for determining appropriate dosages for drugs and toxicity limits. Carbon nanotubes can trigger numerous unusual biological effects, many of which could have unique applications in biotechnology and medicine. However, their resuspension in saline solutions and the accurate determination of their concentration after dispersion in biological media are major handicaps to identify the magnitude of the response of organisms as a function of this exposure. This difficulty has led to inconsistent results and misinterpretations of their in vivo behavior, limiting their potential use in nanomedicine. The lack of a suitable protocol that allows comparing different studies of the content of carbon nanotubes and their adequate resuspension in culture cell media gives rise to this study. Here, we describe a methodology to functionalize, resuspend and determine the carbon nanotube concentration in biocompatible media based on UV-Vis spectroscopy. This method allows us to accurately estimate the concentration of these resuspended carbon nanotubes, after removing bundles and micrometric aggregates, which can be used as a calibration standard, for dosage-dependent studies in biological systems. This method can also be extended to any other nanomaterial to properly quantify the actual concentration. This work has been funded by the Instituto de Salud Carlos III (ISCiii) (ref. PI16/00496, PI19/00349, DTS19/00033); co-funded by ERDF/ESF, “Investing in your future”; the Spanish MINECO (project ref. PGC2018-101464-B-I00) and MICINN NanoBioApp Network (MINECO-17-MAT2016-81955-REDT). Authors also thank the networks Raman4Clinics (BM1401). CRL thanks the MINECO for the Juan de la Cierva Formación grant (ref. FJCI-2015-25306) and LGL the ISCiii for the Sara Borrell grant (ref. CD17/00105). The authors want to also thank the IDIVAL for financial support (refs. NVAL18/07, INNVAL18/28) and technical support.

In vivo imaging and therapy represent one of the most promising areas in nanomedicine. Particularly, the identification and localization of nanomaterials within cells and tissues are key issues to understand their interaction with biological components, namely their cell internalization route, intracellular destination, therapeutic activity and possible cytotoxicity. Here, we show the development of multifunctional nanoparticles (NPs) by providing luminescent functionality to zinc and iron oxide NPs. We describe simple synthesis methods based on modified Stöber procedures to incorporate fluorescent molecules on the surface of oxide NPs. These procedures involve the successful coating of NPs with size-controlled amorphous silica (SiO

In vivo imaging and therapy represent one of the most promising areas in nanomedicine. Particularly, the identification and localization of nanomaterials within cells and tissues are key issues to understand their interaction with biological components, namely their cell internalization route, intracellular destination, therapeutic activity and possible cytotoxicity. Here, we show the development of multifunctional nanoparticles (NPs) by providing luminescent functionality to zinc and iron oxide NPs. We describe simple synthesis methods based on modified Stöber procedures to incorporate fluorescent molecules on the surface of oxide NPs. These procedures involve the successful coating of NPs with size-controlled amorphous silica (SiO2) shells incorporating standard chromophores like fluorescein, rhodamine B or rhodamine B isothiocyanate. Specifically, spherical Fe3O4 NPs with an average size of 10 nm and commercial ZnO NPs (ca. 130 nm), both coated with an amorphous SiO2 shell of ca. 15 and 24 nm thickness, respectively, are presented. The magnetic nanoparticles, with a major presence of magnetite, show negligible coercitivity. Hence, interactions (dipolar) are very weak and the cores are in the superparamagnetic regime. Spectroscopic measurements confirm the presence of fluorescent molecules within the SiO2 shell, making these hybrid NPs suitable for bioimaging. Thus, our coating procedures improve NP dispersibility in physiological media and allow the identification and localization of intracellular ZnO and Fe3O4 NPs using confocal microscopy imaging preserving the fluorescence of the NP. We demonstrate how both Fe3O4 and ZnO NPs coated with luminescent SiO2 are internalized and accumulated in the cell cytoplasm after 24 hours. Besides, the SiO2 shell provides a platform for further functionalization that enables the design of targeted therapeutic strategies. Finally, we studied the degradation of the shell in different physiological environments, pointing out that the SiO2 coating is stable enough to reach the target cells maintaining its original structure. Degradation took place only 24 hours after exposure to different media. Acknowledgements: This work was funded by the following sources: Spanish MINECO projects ref. MAT2015-69508-P, MAT2016-81955-REDT and MAT2017-83631-C3-3-R, NanoBioAp and HIPERNANO Networks (MINECO-17-MAT2016-81955-REDT, RED2018-102626-T), and European Regional Development Fund (ERDF-FEDER) under Projects ref. PI16/00496, EU-FP7 604448 grant, and IDIVAL PREVAL16/02, NVAL16/17 and INNVAL17/11 INNVAL18/28 project. MB-L also thanks the projects NORTE-01-0145-FEDER-028052 (SELF-i), POCI-01-0145-FEDER-028237 (MusclEng) and NORTE-01-0145-FEDER-030171 (NFsCoolingSystem), all in the framework of the Fundação para a Ciência e a Tecnologia (FCT, Portugal). Projects PGC2018-101464-B-I00 (Agencia Estatal de Investigación) and 2014-2020 INTERRED Cooperation Programme Spain–Portugal (POCTEP) through the Project 0624_2IQBIONEURO_6_E are also acknowledged.

International audience; The inorganic chemistry of the Na–Si system at high pressure is fascinating, with a large number of interesting compounds accessible in the industrial pressure scale, below 10 GPa. In particular, Na4Si4 is stable in this whole pressure range and thus plays an important role in understanding the thermodynamics and kinetics underlying materials synthesis at high pressures and high temperatures. In the present work, the melting curve of the Zintl compound Na4Si4 made of Na+ and Si44– tetrahedral cluster ions is studied at high pressures up to 5 GPa, by using in situ electrical measurements. During melting, the insulating Na4Si4 solid transforms into an ionic conductive liquid that can be probed through the conductance of the whole high-pressure cell, i.e., the system constituted of the sample, the heater, and the high-pressure assembly. Na4Si4 melts congruently in the studied pressure range, and its melting point increases with pressure with a positive slope dTm/dp of 20(4) K/GPa.

The inorganic chemistry of the Na-Si system at high pressure is fascinating, with a large number of interesting compounds accessible in the industrial pressure scale, below 10 GPa. In particular, Na

This paper investigates the electronic structure of wurtzite (W) and rock-salt (RS) Zn1-xCoxO nanoparticles (NPs) by means of optical measurements under pressure (up to 25 GPa), X-ray absorption, and transmission electron microscopy. W-NPs were chemically synthesized at ambient conditions and RS-NPs were obtained by pressure-induced transformation of W-NPs. In contrast to the abrupt phase transition in W-Zn1-xCoxO as thin film or single crystal, occurring sharply at about 9 GPa, spectroscopic signatures of tetrahedral Co(2+) are observed in NPs from ambient pressure to about 17 GPa. Above this pressure, several changes in the absorption spectrum reveal a gradual and irreversible W-to-RS phase transition: (i) the fundamental band-to-band edge shifts to higher photon energies; (ii) the charge-transfer absorption band virtually disappears (or overlaps the fundamental edge); and (iii) the intensity of the crystal-field absorption peaks of Co(2+) around 2 eV decreases by an order of magnitude and shifts to 2.5 eV. After incomplete phase transition pressure cycles, the absorption edge of nontransformed W-NPs at ambient pressure exhibits a blue shift of 0.22 eV. This extra shift is interpreted in terms of quantum confinement effects. The observed gradual phase transition and metastability are related to the NP size distribution: the larger the NP, the lower the W-to-RS transition pressure.

The application of nanomaterials in the fields of medicine and biotechnology is of enormous interest, particularly in the areas where traditional solutions have failed. Unfortunately, there is very little information on how to optimize the preparation of nanomaterials for their use in cell culture and on the effects that these can trigger on standard cellular systems. These data are pivotal in nanobiotechnology for the development of different applications and to evaluate/compare the cytotoxicity among the different nanomaterials or studies. The lack of information drives many laboratories to waste resources performing redundant comparative tests that often lead to partial answers due to differences in (i) the nature of the start-up material, (ii) the preparation, (iii) functionalization, (iv) resuspension, (v) the stability/dose of the nanomaterial, etc. These variations in addition to the different analytical systems contribute to the artefactual interpretation of the effects of nanomaterials and to inconsistent conclusions between different laboratories. Here, we present a brief review of a wide range of nanomaterials (nanotubes, various nanoparticles, graphene oxide, and liposomes) with HeLa cells as a reference cellular system. These human cells, widely used as cellular models for many studies, represent a reference system for comparative studies between different nanomaterials or conditions and, in the last term, between different laboratories. This work has been supported by the Spanish MINECO and European FEDER under Project ref. PI16/000496, the NanoBioApp Network Ref. MINECO-17-MAT2016-81955-REDT. We thank IDIVAL for INNVAL15/16, INNVAL 17/11, PREVAL 16/03, 16/02, 17/04, and the Raman4clinics BMBS COST Actions BM1401 and TD1402. We also thank Débora Muñoz for her technical assistance. We are grateful to the Nikon A1R Laser Microscopy Unit and the TEM Unit of the IDIVAL Institute.

International audience; Hexagonal Si allotropes are expected to enhance light absorption in the visible range as compared to common cubic Si with diamond structure. Therefore, synthesis of these materials is crucial for the development of Si-based optoelectronics. In this work, we combine in situ high-pressure high-temperature synthesis and vacuum heating to obtain hexagonal Si. High pressure is one of the most promising routes to stabilize these allotropes. It allows one to obtain large-volume nanostructured ingots by a sequence of direct solid–solid transformations, ensuring high-purity samples for detailed characterization. Thanks to our synthesis approach, we provide the first evidence of a polycrystalline bulk sample of hexagonal Si. Exhaustive structural analysis, combining fine-powder X-ray and electron diffraction, afforded resolution of the crystal structure. We demonstrate that hexagonal Si obtained by high-pressure synthesis correspond to Si-4H polytype (ABCB stacking) in contrast with Si-2H (AB stacking) proposed previously. This result agrees with prior calculations that predicted a higher stability of the 4H form over 2H form. Further physical characterization, combining experimental data and ab initio calculations, have shown a good agreement with the established structure. Strong photoluminescence emission was observed in the visible region for which we foresee optimistic perspectives for the use of this material in Si-based photovoltaics.

Zinc is a crucial element in biology that plays chief catalytic, structural and protein regulatory roles. Excess cytoplasmic Zinc is toxic to the cells so there are cell-entry and intracellular buffering mechanisms that control intracellular Zinc disponibility. Tubulin and actin are two Zinc-scavenging proteins that are essential components of the cellular cytoskeleton implicated in cell division, migration and cellular architecture maintenance. Here we demonstrate how exposure to different ZnO nanostructures, namely ZnO commercial nanoparticles and custom-made ZnO nanowires, produce acute cytotoxic effects in human keratinocytes (HaCat) and epithelial cells (HeLa) triggering a dose-dependent cell retraction and collapse. We show how engulfed ZnO nanoparticles dissolve intracellularly, triggering actin filament bundling and structural changes in microtubules, transforming these highly dynamic 24nm diameter polymers into rigid macrotubes of tubulin, severely affecting cell proliferation and survival. Our results demostrate that nano-ZnO causes an acute cytoskeletal collapse that triggers necrosis, followed by a late reactive oxygen species (ROS)-dependent apoptotic process. This work has been supported by the Spanish ISCIII-MINECO under Projects ref. PI13/01074, AES 2013; FONDOS FEDER; MAT2012-38664-C02-01. We especially thank the IDIVAL for their support to LGH and the IDIVAL-Microscopy Unit for all the microscopy imaging.

High-pressure techniques make possible to investigate the changes in the electronic properties induced by modifications of the local or crystal structure of the material without changing the chemical composition. The different sensitivity of excited states to crystal-field strength enables energy tuning of the states, which are eventually responsible for the optical properties. It is possible to induce resonance between levels producing exotic effects like upconversion as well as excited state crossover or high-spin to low-spin transitions. Herein, we present selected examples of high-pressure effect for understanding luminescent phenomena or even inducing new ones.

We have studied the thin film morphology of a semiconducting polymer photovoltaic blend comprising an electron acceptor poly(9,9-dioctylfluorene-co-benzothiadiazole) (F8BT) and the donor poly(9,9′-dioctylfluorene-co-bis-N,N′-(4-butylphenyl)-bis-N,N′-phenyl-1,4 phenylenediamine) (PFB). The molecular weight and blend weight ratio of the constituent polymers were used to modify the morphology. The average chemical composition of the bulk of F8BT:PFB blend in thin films was mapped using Raman microscopy at different depths from the air-film interface through controlled successive etching from the upper surface layer using an oxygen plasma. Correlating the lateral to the vertical Raman analysis of the phase separation of the film (blend weight ratio of 50:50) reveals that the μm scale de-mixed lateral phase structure seen on the free surface is present throughout most of the film thickness, though there is also some F8BT content within the PFB-rich wetting layer on the glass substrate, which we consider is due to the F8BT-rich interface at the surface to the substrate. The dependence of photovoltaic performance on morphology is discussed.

An explanation for the puzzling absence of luminescence from the Pr3+ 3PJ[=0,1,2] states in C-Ln2O3 (cubic; Ln3+=Lu3+, Y3+, Gd3+) family of materials is provided by conducting a study of the emission properties of C-Y2O3:Pr3+ under applied hydrostatic pressure. Above 7 GPa, electronic transitions from the Pr3+ 3PJ[=0,1,2] states are observed in the emission spectrum of C-Y2O3:Pr3+ at room temperature and below. The experimental data reveal that the crystal-field split Pr3+ 4f15d1 configuration is located entirely within the host lattice conduction band and that the promotion of the electron to the Pr3+ 4f15d1 state produces a self-trapped exciton-like state with the configuration, [Pr4++eCB], where eCB indicates an electron in the host lattice conduction band. Upon excitation, the exciton-like state bypasses the upper emitting 3PJ[=0,1,2] states and directly feeds the lower emitting 1D2 state. This explains the absence of optical transitions from the Pr3+ 3PJ[=0,1,2] states in the emission spectrum of C-Y2O3:Pr3+ at ambient pressure. At high pressures, emission transitions from the Pr3+ 3PJ[=0,1,2] states are observed because of the localization of the Pr3+ 4f15d1 state to below the host lattice conduction band edge.

This work investigates the electronic structure and photoluminescence properties of Co2+-doped ZnO and their pressure and temperature dependences through high-resolution absorption and emission spe...

Site-selective spectroscopy in hexagonal β-NaYF4:Er 3+,Yb3+ has revealed different environments for Er 3+ ions (multisite formation). The low-temperature 4S 3/2 → 4I15/2 Er3+green emission depends on the excitation wavelength associated with the 4F 7/2 Er3+ level. We have studied the effect of hydrostatic pressure on the green, red, and blue Er3+ emission upon NIR excitation at ∼980 nm, in order to establish the role played by energy resonance conditions and the multiple Er3+ sites due to the disordered structure for the upconversion (UC) process (energy tuning). The variation of photoluminescence spectra and lifetimes as a function of pressure and temperature reveals that the origin of the high green UC efficiency of the β-NaYF4:Er3+,Yb3+ compound is mainly due to the multisite distribution, and the low phonon energy of the host lattice. © 2011 American Chemical Society., This work was financially supported by the Spanish Ministerio de Ciencia e Innovación (MICINN) (under Project No. MAT2008-06873-C02-01) and by the MALTA-CONSOLIDER INGENIO 2010 Project (Ref. No. CSD2007-00045). The author also thanks the Spanish MICINN for a FPI research grant (Ref. No. BES-2009-013434).

We report a simple synthesis of ultra-thin lanthanide oxide nanowires and ribbons via the autoclave-based decomposition of lanthanide oleates within passivating surfactants. Electron microscopy reveals the formation of linear self assemblies of lanthanide oxide nanoparticles that subsequently recrystallize into high aspect ratio materials via an “imperfect oriented attachment” mechanism.