ConspectusLanthanide-doped upconverting nanoparticles (UCNPs) convert near-infrared (NIR) light into visible emission through multiphoton absorption processes. This property has made them useful tools for sensing and single-particle studies in biological environments. Their characteristic narrow emission lines, resistance to photobleaching, and the thermal coupling between the excited states of trivalent erbium (Er3+) have positioned UCNPs as a practical platform for intracellular thermometry despite their moderate sensitivity. Their response can be measured with standard microscopes using inexpensive NIR excitation sources, enabling experiments that are not easily achieved with other types of nanoscale thermometers. However, using UCNPs inside living cells also reveals important limitations because the intracellular medium is chemically complex and may alter the emission properties that form the basis of the thermal readout. Variations in local pH, ion concentration, viscosity, or molecular crowding can shift energy levels or modify nonradiative relaxation pathways. As a result, establishing the reliability of UCNP thermometry inside cells requires dedicated studies on particle stability, surface chemistry, and the influence of the cytoplasmic environment. Understanding these effects is essential for determining whether ratiometric UCNP thermometry can serve as a quantitative intracellular tool rather than only a qualitative indicator of heating. UCNPs have also enabled new single-particle experiments through optical trapping. A tightly focused NIR beam can immobilize an individual nanoparticle while simultaneously exciting its upconversion emission, allowing continuous monitoring of spectral changes, rotational dynamics, and local mechanical properties. These studies provide access to information that is hidden in ensemble measurements, such as particle-particle radiative interactions or the coupling between particle rotation/movement and local viscosity. Yet optical trapping also brings its own challenges: the forces acting on sub-100 nm UCNPs are modest, and trapping stability is strongly affected by laser-induced heating. Increasing dopant concentration improves confinement but raises thermal load, leading to a trade-off that must be carefully balanced. Approaches based on plasmonic enhancement are not suitable due to their additional heating, motivating interest in alternative photonic structures such as dielectric metasurfaces that could strengthen confinement while keeping temperatures low. Together, intracellular thermometry and single-particle trapping illustrate both the strengths and the current limitations of UCNPs. Their optical properties make them accessible probes for measuring local temperature and mechanical responses, but their performance heavily depends on the surrounding environment. In this Account, we summarize our efforts to understand UCNP behavior under realistic biological and trapping conditions. We discuss the stability of the thermometric response inside cells, the confinement-heating balance in optical traps, and the opportunities offered by single-particle measurements for studying light-matter interactions at the nanoscale. These considerations outline a path toward more reliable sensing and manipulation strategies based on UCNPs.

All-optical theranostic systems are sought after in nanomedicine, since they combine in a single platform therapeutic and diagnostic capabilities. Commonly in these systems the therapeutic and diagnostic/imaging functions are accomplished with plasmonic photothermal agents and luminescent nanoparticles (NPs), respectively. For maximized performance and minimized side effects, these two modalities should be independently activated, i.e., in a decoupled way, using distinct near infrared (NIR) wavelengths: a radiation window wherein photon-tissue interaction is reduced. Yet, to date, a fully decoupled NIR theranostics system is not available. Finding plasmonic NPs working in that range and without spectral overlap with the absorption and emission of state-of-the-art NIR luminescent NPs requires the development of new materials specifically designed for this purpose. To address this limitation, we herein present water-dispersible indium tin oxide (ITO) NPs whose surface plasmon resonance was tuned for exclusive operation in the third biological window (NIR-III, 1500-1800 nm). That leaves available the first and second biological windows, in which diagnostic tools are typically working. Both the microwave-assisted synthesis and the water-transfer protocol were optimized to obtain NPs with maximum light-to-heat conversion capabilities, owing to their small size and reduced aggregation in aqueous media. Proof-of-concept experiments showed that the lack of overlap between the absorption of ITO NPs and the absorption/emission of model near infrared luminescent species (the widely used Nd3+-doped NPs) is an asset when devising an all-optical theranostics platform. The obtained results set the stage for the development of a new generation of high-performance, all-optical theranostic systems with minimized side effects.

Two‐dimensional (2D) semiconductor materials are being explored for applications including photocatalysis and optoelectronic devices. This class of materials features high surface‐to‐volume ratio that imparts unique physical properties. Yet, this feature makes 2D semiconductor materials prone to chemical changes that translate to variations in their photophysical behavior. Large‐scale application of these materials requires an understanding of degradation processes toward developing strategies to increase their stability. Here, the effect of air exposure on underexplored 2D semiconductor material γ‐In2S3 is studied. This In2S3 polymorph is stabilized as nanoplatelets, which are then characterizes before and after exposure to air. A marked surface oxidation , accompanied by drastic variations in photoluminescence is observed. Temperature‐dependent spectroscopic measurements show that the emission spectrum of fresh γ‐In2S3 nanoplatelets is dominated by two defect‐related bands, while oxidation enhances the contribution of a third band. An energy level scheme is proposed based on the analysis of the spectroscopic data. This study finally portrays how a postsynthesis treatment with an oxygen‐containing molecule (oleic acid) changes the photoluminescence of γ‐In2S3 nanoplatelets similarly to a prolonged air exposure. The work shines light on the optical properties of γ‐In2S3, paving the way for their control and the use of this material in luminescence sensing.

Semiconductor materials capable of hosting luminescent lanthanide ions (Ln3+) and sensitize their emission are scarce. Halide perovskites are prime systems for this purpose, yet they often feature toxic elements (e.g., lead) in their composition and have reduced stability. The discovery of alternative semiconductors that feature host-to-Ln3+ energy transfer mechanisms - while being more stable and environmentally benign - would thus broaden the applicability of this class of luminescent materials. Herein, we report near-infrared (NIR) emitting phosphors made of BaZrS3 chalcogenide perovskite doped with Ln3+ ions (Ln = Yb, Er, Nd). We chose BaZrS3 because it features (i) crystallographic sites that can accommodate Ln3+ ions, (ii) high light absorption coefficient in the visible, and (iii) stability. The phosphors were prepared via sulfurization of Ln3+-doped BaZrO3 microparticles obtained by a microwave-assisted procedure. The so-obtained Ln3+-doped BaZrS3 display low-temperature NIR emission characteristic of each Ln3+ ion when exciting the matrix. Following photoluminescence studies on doped and undoped BaZrS3 as a function of temperature, we propose an energy level scheme that explains the rich NIR photoluminescence displayed by these phosphors. The obtained results pave the way for the optimization of Ln3+-doped BaZrS3 for optical applications and are expected to spur the study of other ternary chalcogenides sensitization of Ln3+ luminescence.

Mechanical forces control the function of organisms and mediate the interaction between biological systems and their environments. Knowledge of these forces will increase the understanding of biological processes and can support the development of novel diagnostic and therapeutic procedures. Although techniques like atomic force microscopy and droplet insertion method allow measuring forces over a broad range of values, they are invasive and lack versatility. A promising way to overcome these hurdles is luminescent nanomanometry. Quantum dots (QDs) specifically have optical properties that depend on their size because of the quantum confinement, which makes them responsive to applied forces. Yet, a fine understanding of how fundamental parameters affect the response to applied stress is required before a QD family can be credibly proposed as luminescent nanomanometers. Here, a thorough study is conducted on how size and stoichiometry affect the nanomanometry performance of CuInS2 QDs. The studied QDs feature pressure-dependent photoluminescence in the red/near-infrared range, which can enable the measurement of mechanical forces in the range of physiological relevance in a remote and minimally invasive way. It is shown that tuning size and stoichiometry can simultaneously enhance the CuInS2 QDs' brightness and response to applied pressure, thus providing guidelines for better luminescent nanomanometers.

Among luminescent nanostructures actively investigated in the last couple of decades, rare earth (RE3+) doped nanoparticles (RENPs) are some of the most reported family of materials. The development of RENPs in the biomedical framework is quickly making its transition to the ∼800 nm excitation pathway, beneficial for both in vitro and in vivo applications to eliminate heating and facilitate higher penetration in tissues. Therefore, reports and investigations on RENPs containing the neodymium ion (Nd3+) greatly increased in number as the focus on ∼800 nm radiation absorbing Nd3+ ion gained traction. In this review, we cover the basics behind the RE3+ luminescence, the most successful Nd3+-RENP architectures, and highlight application areas. Nd3+-RENPs, particularly Nd3+-sensitized RENPs, have been scrutinized by considering the division between their upconversion and downshifting emissions. Aside from their distinctive optical properties, significant attention is paid to the diverse applications of Nd3+-RENPs, notwithstanding the pitfalls that are still to be addressed. Overall, we aim to provide a comprehensive overview on Nd3+-RENPs, discussing their developmental and applicative successes as well as challenges. We also assess future research pathways and foreseeable obstacles ahead, in a field, which we believe will continue witnessing an effervescent progress in the years to come.

Rare-earth doped nanoparticles (RENPs) are attracting increasing interest in materials science due to their optical, magnetic, and chemical properties. RENPs can emit and absorb radiation in the second biological window (NIR-II, 1000-1400 nm) making them ideal optical probes for photoluminescence (PL) in vivo imaging. Their narrow emission bands and long PL lifetimes enable autofluorescence-free multiplexed imaging. Furthermore, the strong temperature dependence of the PL properties of some of these RENPs makes remote thermal imaging possible. This is the case of neodymium and ytterbium co-doped NPs that have been used as thermal reporters for in vivo diagnosis of, for instance, inflammatory processes. However, the lack of knowledge about how the chemical composition and architecture of these NPs influence their thermal sensitivity impedes further optimization. To shed light on this, we have systematically studied their emission intensity, PL decay time curves, absolute PL quantum yield, and thermal sensitivity as a function of the core chemical composition and size, active-shell, and outer-inert-shell thicknesses. The results revealed the crucial contribution of each of these factors in optimizing the NP thermal sensitivity. An optimal active shell thickness of around 2 nm and an outer inert shell of 3.5 nm maximize the PL lifetime and the thermal response of the NPs due to the competition between the temperature-dependent back energy transfer, the surface quenching effects, and the confinement of active ions in a thin layer. These findings pave the way for a rational design of RENPs with optimal thermal sensitivity.

The application of nanoparticles in the biological context generally requires their dispersion in aqueous media. In this sense, luminescent nanoparticles are an excellent choice for minimally invasive imaging and local temperature sensing (nanothermometry). For these applications, nanoparticles must operate in the physiological temperature range (25–50 °C) but also in the near‐infrared spectral range (750–1800 nm), which comprises the three biological windows of maximal tissue transparency to photons. In this range, water displays several absorption bands that can strongly affect the optical properties of the nanoparticles. Therefore, a full understanding of the temperature dependence of water absorption in biological windows is of paramount importance for applications based on these optical properties. Herein, the absorption spectrum of water in the biological windows over the 25–65 °C temperature range is systematically analyzed, and its temperature dependence considering the coexistence of two states of water is interpreted. Additionally, to illustrate the importance of state‐of‐the‐art applications, the effects of the absorption of water on the emission spectrum of Ag2S nanoparticles, the most sensitive luminescent nanothermometers for in vivo applications to date, are presented. The spectral shape of the nanoparticles’ emission is drastically affected by the water absorption, impacting their thermometric performance.

Ideally, any material used should be nontoxic and produced with safe, inexpensive, and energy‐effective processes. In the case of optically active nanoparticles, this is often not the case, as they are frequently composed of hazardous heavy metals and/or produced with methods far from being environmentally friendly. Herein, the preparation of Ag2S‐based nanoparticles via a simple green synthesis route is explored. Aqueous extracts of roasted coffee are used as sources of coordinating molecules. Optimization of the reaction conditions yields dimeric Ag−Ag2S nanoparticles, whose near‐infrared photoluminescence can be switched on via H2O2‐mediated oxidation. This oxidation transforms suitable photoacoustic contrast agents into fluorescence imaging probes. Theoretical calculations further clarify the role of metallic silver in determining the optical properties of Ag2S. Overall, it is demonstrated that nanomaterials with tangible applicative potential can be prepared via cost‐ and energy‐effective synthesis strategies that entail benign, renewable chemicals.

AbstractTemperature touches all aspects of our daily life, including climate, production plants, food storage, transportation, metrology, microelectronics, and medicine, and is a major factor dictating performance of nanotechnologies.1-4However, while the heat transfer is well understood in bulk, neither experimental nor theoretical models provide a complete picture of the thermal dynamics at the nanoscale.5-7Here, in situ luminescence thermometry is used to probe the heat propagation taking place within lanthanide (Ln3+)-doped upconverting nanoparticles (UCNPs). We have designed UCNPs with Er3+and Tm3+thermometric layers positioned at different locations relative to their surface, varying the distance a heat wave travels before encountering the layers. Despite being separated only by a few tens of nanometers, the thermometric layer closer to the surface of UCNPs detects temperature increase much earlier than the one located at the center – yielding the heat propagation speed in UCNPs ~1.3 nm/s. The UCNPs featuring the two thermometric layers in a single nanostructure confirmed the above result and allowed us to uncover diffusive and non-diffusive (ballistic) heat transport regimes, as well as their interplay and complex heat exchange dynamics taking place in colloidal nanoparticles (nanofluids) at a room temperature.

Temperature of tissues and organs is one of the first parameters affected by physiological and pathological processes, such as metabolic activity, acute trauma, or infection-induced inflammation. Therefore, the onset and development of these processes can be detected by monitoring deviations from basal temperature. To accomplish this, minimally invasive, reliable, and accurate measurement of the absolute temperature of internal organs is required. Luminescence nanothermometry is the ideal technology for meeting these requirements. Although this technique has lately undergone remarkable developments, its reliability is being questioned due to spectral distortions caused by biological tissues. In this work, how the use of bright Ag2 S nanoparticles featuring temperature-dependent fluorescence lifetime enables reliable and accurate measurement of the absolute temperature of the liver in mice subjected to lipopolysaccharide-induced inflammation is demonstrated. Beyond the remarkable thermal sensitivity (≈ 3% °C-1 around 37 °C) and thermal resolution obtained (smaller than 0.3 °C), the results included in this work set a blueprint for the development of new diagnostic procedures based on the use of intracorporeal temperature as a physiological indicator.

Minimally invasive monitoring of brain activity is essential not only to gain understanding on the working principles of the brain, but also for the development of new diagnostic tools. In this perspective we describe how brain thermometry could be an alternative to conventional methods (e.g., magnetic resonance or nuclear medicine) for the acquisition of thermal images of the brain with enough spatial and temperature resolution to track brain activity in minimally perturbed animals. We focus on the latest advances in transcranial luminescence thermometry introducing a critical discussion on its advantages and shortcomings. We also anticipate the main challenges that the application of luminescent nanoparticles for brain thermometry will face in next years. With this work we aim to promote the development of near infrared luminescence for brain activity monitoring, which could also benefit other research areas dealing with the brain and its illnesses.

Luminescence thermometry is a spectroscopic technique for remote temperature detection based on the thermal dependence of the luminescence of phosphors, presenting numerous applications ranging from biosciences to engineering. In this work, we use the Er 3+ emission of the NaGdF 4 /NaGdF 4 :Yb 3+ ,Er 3+ /NaGdF 4 upconverting nanoparticles upon 980 nm laser excitation to determine simultaneously the absolute temperature and the excitation power density. The Er 3+ 2 H 11/2 → 4 I 15/2 and 4 S 3/2 → 4 I 15/2 emission bands, which are commonly used for thermometric purposes, overlap with the 2 H 9/2 → 4 I 13/2 emission band, which can lead to erroneous temperature readout. Applying the concept of luminescent primary thermometry to resolve the overlapping Er 3+ transitions, a dual nanosensor synchronously measuring the temperature and the delivered laser pump power is successfully realized holding promising applications in laser-supported thermal therapies.

The exciting advancements that we are currently witnessing in terms of novel materials and synthesis approaches are leading to the development of colloidal nanoparticles (NPs) with increasingly greater tunable properties. We have now reached a point where it is possible to synthesize colloidal NPs with functionalities tailored to specific societal demands. The impact of this new wave of colloidal NPs has been especially important in the field of biomedicine. In that vein, luminescent NPs with improved brightness and near-infrared working capabilities have turned out to be optimal optical probes that are capable of fast and high-resolution in vivo imaging. However, luminescent NPs have thus far only reached a limited portion of their potential. Although we believe that the best is yet to come, the future might not be as bright as some of us think (and have hoped!). In particular, translation of NP-based fluorescence imaging from preclinical studies to clinics is not straightforward. In this Perspective, we provide a critical assessment and highlight promising research avenues based on the latest advances in the fields of luminescent NPs and imaging technologies. The disillusioned outlook we proffer herein might sound pessimistic at first, but we consider it necessary to avoid pursuing "pipe dreams" and redirect the efforts toward achievable-yet ambitious-goals.

Deliberate and local increase of the temperature within solid tumors represents an effective therapeutic approach. Thermal therapies embrace this concept leveraging the capability of some species to convert the absorbed energy into heat. To that end, magnetic hyperthermia (MHT) uses magnetic nanoparticles (MNPs) that can effectively dissipate the energy absorbed under alternating magnetic fields. However, MNPs fail to provide real-time thermal feedback with the risk of unwanted overheating and impeding on-the-fly adjustment of the therapeutic parameters. Localization of MNPs within a tissue in an accurate, rapid, and cost-effective way represents another challenge for increasing the efficacy of MHT. In this work, MNPs are combined with state-of-the-art infrared luminescent nanothermometers (LNTh; Ag2 S nanoparticles) in a nanocapsule that simultaneously overcomes these limitations. The novel optomagnetic nanocapsule acts as multimodal contrast agents for different imaging techniques (magnetic resonance, photoacoustic and near-infrared fluorescence imaging, optical and X-ray computed tomography). Most crucially, these nanocapsules provide accurate (0.2 °C resolution) and real-time subcutaneous thermal feedback during in vivo MHT, also enabling the attainment of thermal maps of the area of interest. These findings are a milestone on the road toward controlled magnetothermal therapies with minimal side effects.

Neodymium-doped yttrium aluminum garnet (YAG:Nd3+) has been widely developed during roughly the past 60 years and has been an outstanding fluorescent material. It has been considered as the gold standard among multipurpose solid-state lasers. Yet, the successful downsizing of this system into the nanoregimen has been elusive, so far. Indeed, the synthesis of a garnet structure at the nanoscale, with enough crystalline quality for optical applications, was found to be quite challenging. Here, we present an improved solvothermal synthesis method producing YAG:Nd3+ nanocrystals of remarkably good structural quality. Adequate surface functionalization using asymmetric double-hydrophilic block copolymers, constituted of a metal-binding block and a neutral water-soluble block, provides stabilized YAG:Nd3+ nanocrystals with long-term colloidal stability in aqueous suspensions. These newly stabilized nanoprobes offer spectroscopic quality (long lifetimes, narrow emission lines, and large Stokes shifts) close to that of bulk YAG:Nd3+. The narrow emission lines of YAG:Nd3+ nanocrystals are exploited by differential infrared fluorescence imaging, thus achieving an autofluorescence-free in vivo readout. In addition, nanothermometry measurements, based on the ratiometric fluorescence of the stabilized YAG:Nd3+ nanocrystals, are demonstrated. The progress here reported paves the way for the implementation of this new stabilized YAG:Nd3+ system in the preclinical arena.

The emergence of luminescence nanothermometry in bio and nanomedicine has enabled achievements outside the reach of conventional techniques. For instance, it has provided real‐time monitoring of in vivo thermal therapies of tumors, a mandatory requirement for these techniques to work safely and efficiently. However, the reliability of intratumoral thermal readings is currently in question due to the presence of artefacts caused by the inhomogeneous optical properties of biological tissues. This work demonstrates how it is possible to avoid, under specific conditions, these artefacts and reach precise and reliable in vivo intratumoral thermal feedback during in vivo photothermal treatments. The method proposed is based on the use of luminescent nanoparticles capable of multiparametric thermal sensing. The results demonstrate how the convergence of the different thermal readouts becomes a solid indicator of their reliability. It is shown how this new approach makes possible precise (thermal uncertainties below 1 °C) intratumoral thermal feed‐back, while simple, efficient, and minimally invasive in vivo thermal treatments of surface tumors is carried out. Results included in this work provide an ingenious route toward the consolidation of luminescence nanothermometry as a convincing technique for high sensitivity preclinical thermal sensing, while also constituting a step toward improved photothermal therapies.

Lanthanide-doped nanoparticles (LnNPs) are versatile near-infrared (NIR) emitting nanoprobes that have led to their growing interest for use in biomedicine-related imaging. Toward the brightest LnNPs, high photoluminescence quantum yield (PLQY) values are attained by implementing core/shell engineering, particularly with an optically inert shell. In this work, a thorough investigation is performed to quantify how an outer inert shell maintains the PLQY of Nd3+-doped LnNPs dispersed in an aqueous environment. Three relevant quantitative findings affecting the PLQY of Nd3+-doped LnNPs are identified: (i) the PLQY of core LnNPs is improved 3-fold upon inert shell coating; (ii) PLQY decreases with increasing Nd3+ doping despite the inert shell; and (iii) solvent quenching has a major influence on the PLQY of the LnNPs, though it is relatively lessened for high Nd3+ doping. Overall, we shed new light on the impact of the LnNP architecture on the NIR emission, as well as on the quenching effects caused by doping concentration and solvent molecules.

Lanthanide-doped nanoparticles (LNPs) are speedily colonizing several research fields, such as biological (multimodal) imaging, photodynamic therapy, volumetric encoding displays, and photovoltaics. Yet, the electronic transitions of lanthanide ions obey the Laporte rule, which dramatically hampers their light absorption capabilities. As a result, the brightness of these species is severely restricted. This intrinsic poor absorption capability is the fundamental obstacle for untapping the full potential of LNPs in several of the aforementioned fields. Among others, three of the most promising physicochemical approaches that have arisen during last two decades to face the challenges of increasing LNP absorption are plasmonic enhancement, organic-dye sensitization, and coupling with semiconductors. The fundamental basis, remarkable highlights, and comparative achievements of each of these pathways for absorption enhancement are critically discussed in this minireview, which also includes a detailed discussion of the exciting perspectives ahead.