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The directed migration of cellular clusters enables morphogenesis, wound healing and collective cancer invasion. Gradients of substrate stiffness direct the migration of cellular clusters in a process called collective durotaxis, but the underlying mechanisms remain unclear. Here we unveil a connection between collective durotaxis and the wetting properties of cellular clusters. We show that clusters of cancer cells dewet soft substrates and wet stiff ones. At intermediate stiffness—at the crossover from low to high wettability—clusters on uniform-stiffness substrates become maximally motile, and clusters on stiffness gradients exhibit optimal durotaxis. Durotactic velocity increases with cluster size, stiffness gradient and actomyosin activity. We demonstrate this behaviour on substrates coated with the cell–cell adhesion protein E-cadherin and then establish its generality on substrates coated with extracellular matrix. We develop an active wetting model that explains collective durotaxis in terms of a balance between in-plane active traction and tissue contractility and out-of-plane surface tension. Finally, we show that the distribution of cluster displacements has a heavy tail, with infrequent but large cellular hops that contribute to durotactic migration. Our study demonstrates a physical mechanism of collective durotaxis, through both cell–cell and cell–substrate adhesion ligands, based on the wetting properties of active droplets.

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.

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).

Nanometric magnetic iron oxide nanoparticles are very useful for biotechnological applications. We are interested in their use for the detection and control of the pathogenic fungus Fusarium oxysporum. Many F. oxysporum formae especiales are a major concern for agriculture and food industry, as they can infect a number of major crops (cereals, potato, etc.) and produce mycotoxins that may give rise to allergic symptoms or be carcinogenic in long-term consumption. These soil borne pathogens can survive as thick-walled chlamydospores, which remain viable in the soil for many years and hence control is problematic. In addition, several ff. spp. are non-pathogenic and even beneficial for agriculture exerting a bio-control effect on other pathogenic strains. Therefore it is crucial to provide control methods effective and directed to the pathogenic ff. spp. We present the synthesis and characterization of superparamagnetic magnetite nanoparticles as well as a functionalization strategy, necessary for the study of the nanoparticles internalization by the Fusarium spp. Superparamagnetic Fe3O4 nanoparticles coated with an ultra-thin (~1 nm) MgO layer (total size ¿ 25 nm and hydrodynamic diameter ¿ 30 nm) have been synthesized combining co-precipitation and sol-gel methods. A thorough chemical and structural characterization has been carried out by HRTEM, XRD, EDS, DLS and TGA. Aberration corrected HRTEM experiments with sub-angstrom spatial resolution have allowed us to distinguish the ultra-thin MgO shell that grows epitaxially on the magnetic cores. The MgO shell protects the magnetic nuclei from oxidation, preserving the superparamagnetism even after calcination at high temperatures (¿ 600ºC)1. To improve their water stability and to obtain a suitable surface for biochemical functionalization, our synthesized particles have been encapsulated in an aminated silica coating (also through a sol-gel process). After that the particles were bio-functionalized with G protein/ant

Enzymes are selective, specific, efficient, and more sustainable catalysts than their chemical counterparts. From an industrial perspective, multienzymatic systems to produce chemical compounds are particularly attractive since they comply with most green production principles including the minimization of wastes and their ecological footprints. However, the number of industrial processes based on the use of enzymes as catalysts remains limited. Indeed, incompatibility issues of enzymes with respect to reaction conditions or cross-reactivity are still challenging aspects that make one-pot enzyme cascade reactions hard to perform. The urgent need for more sustainable industrial processes has made different research fields, not accustomed to working together, join efforts to develop innovative technologies that could be key enabling to overcome these challenges. Among these technologies are those that seek to synergistically integrate the specific recognition and unique catalytic properties of enzymes with the size-dependent unique properties of nanoparticles. However, rather than giving a complete overview of the use of nanomaterials in biocatalysts, here it will be discussed the feasibility of triggering magnetic nanoparticles (MNPs) into hotspots by remote nanoactuation for the thermal modulation of discrete enzyme molecules activity with minimal collateral heating., The possibility of heating discrete and defined local regions within a sample offers the potential to introduce a game-changing breakthrough in industrial biocatalysis by achieving coordinated enzyme function and thus concurrent multienzyme reactions. Therefore, not only the principles behind the activation of MNPs as hotspots, but also those examples that report the selective control of enzyme activity by magnetic heating, together with the foreseen challenges for the transfer of this technology to the industry, will be discussed.

Gastric cancer (GC) is one of the commonest cancers with high morbidity and mortality in the world. How to realize precise diagnosis and therapy of GC owns great clinical requirement. In recent years, artificial intelligence (AI) has been actively explored to apply to early diagnosis and treatment and prognosis of gastric carcinoma. Herein, we review recent advance of AI in early screening, diagnosis, therapy and prognosis of stomach carcinoma. Especially AI combined with breath screening early GC system improved 97.4 % of early GC diagnosis ratio, AI model on stomach cancer diagnosis system of saliva biomarkers obtained an overall accuracy of 97.18 %, specificity of 97.44 %, and sensitivity of 96.88 %. We also discuss concept, issues, approaches and challenges of AI applied in stomach cancer. This review provides a comprehensive view and roadmap for readers working in this field, with the aim of pushing application of AI in theranostics of stomach cancer to increase the early discovery ratio and curative ratio of GC patients.

Nanozymes with inherent enzyme-mimicking catalytic properties combat malignant tumor progression via catalytic therapy, while the therapeutic efficacy still needs to be improved. In this work, ultrasmall platinum nanozymes (nPt) in a confined domain of a wormlike pore channel in gold nanobipyramidal–mesoporous silica dioxide nanocomposites, producing nanozyme carriers AP-mSi with photoenhanced peroxidase ability, are innovatively synthesized. Afterward, based on the prepared AP-mSi, a lung-cancer nanozymes probe (AP-HAI) is ingeniously produced by removing the SiO2 template, modifying human serum albumin, and loading atovaquone molecules (ATO) as well as IR780. Under NIR light irradiation, inner AuP and IR780 collaborate for photothermal process, thus facilitating the peroxidase-like catalytic process of H2O2. Additionally, loaded ATO, a cell respiration inhibitor, can impair tumor respiration metabolism and cause oxygen retention, hence enhancing IR780's photodynamic therapy (PDT) effectiveness. As a result, IR780's PDT and nPt nanozymes' photoenhanced peroxidase-like ability endow probes a high ROS productivity, eliciting antitumor immune responses to destroy tumor tissue. Systematic studies reveal that the obvious reactive oxygen species (ROS) generation is obtained by the strategy of using nPt nanozymes and reducing oxygen consumption by ATO, which in turn enables lung-cancer synergetic catalytic therapy/immunogenic-cell-death-based immunotherapy. The results of this work would provide theoretical justification for the practical use of photoenhanced nanozyme probes.

Herein, we have developed nanohybrids (nHs) to remotely activate a therapeutic enzyme for its use in Directed Enzyme Prodrug Therapy (DEPT). The coencapsulation of magnetic nanoparticles (MNPs) with horseradish peroxidase (HRP) using biomimetic silica as an entrapment matrix was optimized to obtain nanosized hybrids (∼150 nm) for remote activation of the therapeutic enzyme. HRP converts indole-3-acetic acid (3IAA) into peroxylated radicals, whereas MNPs respond to alternating magnetic fields (AMFs) becoming local hotspots. The AMF application triggered an increase in the bioconversion rate of HRP matching the activity displayed at the optimal temperature of the nHs (Topt = 50 °C) without altering the temperature of the reaction media. This showed that enzyme nanoactuation is possible with MNPs even if they are not covalently bound. After an extensive physicochemical/magnetic characterization, the spatial location of each component of the nH was deciphered, and an insulating role of the silica matrix was suggested as critical for introducing remote control over HRP. In vitro assays, using a human pancreatic cancer cell line (MIA PaCa-2), showed that only upon exposure to AMF and in the presence of the prodrug, the enzyme-loaded nHs triggered cell death. Moreover, in vivo experiments showed higher reductions in the tumor volume growth in those animals treated with nHs in the presence of 3IAA when exposed to AMF. Thus, this work demonstrates the feasibility of developing a spatiotemporally controlled DEPT strategy to overcome unwanted off-target effects.

Superparamagnetic iron oxide nanoparticles have hogged the limelight in different fields of nanotechnology. Surprisingly, notwithstanding the prominent role played as agents in magnetic hyperthermia treatments, the effects of nanoparticle size and shape on the magnetic hyperthermia performance have not been entirely elucidated yet. Here, spherical or cubical magnetic nanoparticles synthesized by a thermal decomposition method with the same magnetic and hyperthermia properties are evaluated. Interestingly, spherical nanoparticles displayed significantly higher magnetic relaxivity than cubic nanoparticles; however, comparable differences were not observed in specific absorption rate (SAR), pointing out the need for additional research to better understand the connection between these two parameters. Additionally, the as-synthetized spherical nanoparticles showed negligible cytotoxicity and, therefore, were tested in vivo in tumor-bearing mice. Following intratumoral administration of these spherical nanoparticles and a single exposure to alternating magnetic fields (AMF) closely mimicking clinical conditions, a significant delay in tumor growth was observed. Although further in vivo experiments are warranted to optimize the magnetic hyperthermia conditions, our findings support the great potential of these nanoparticles as magnetic hyperthermia mediators for tumor therapy.

Magnetic nanoparticles (MNPs) are widely used for immobilizing complex biomolecules such as proteins due to their high loading capacity, biocompatibility, and easy magnetic harvesting. However, there is not a universal solution to achieve the oriented immobilization of the protein of interest. One common strategy involves the selective binding of poly-histidine-tagged (His-tag) proteins to divalent transition metal centers (TM2+) chelated by organic molecules like nitrilotriacetic acid (NTA). This article describes an innovative procedure to functionalize MNPs by simply growing of a thin layer of TM2+ hydroxides on the MNP surface, which increases the number of coordination centers and enhances the surface interaction with the protein surface. The immobilization yields of two sets of MNPs coated with Co2+, Ni2+ and Cu2+ hydroxides were compared to the conventional coating using the same inorganic cores but coated and functionalized with NTA-TM2+ moieties. It is shown that the one-step Co coated MNPs showed the highest selectivity and specificity towards His-tags. Thus, this coating not only reduce the functionalization steps to drive an oriented protein binding but also achieve an increment of immobilization yields over 1.5-fold respect to NTA-Co2+ analogous for his-tagged proteins with different 3D complexity while preserving similar or even higher enzymatic activity.

Oriented and covalent immobilization of proteins on magnetic nanoparticles (MNPs) is particularly challenging as it requires both the functionality of the protein and the colloidal stability of the MNPs to be preserved. Here, we describe a simple, straightforward, and efficient strategy for MNP functionalization with proteins using metal affinity binding. Our method involves a single-step process where MNPs are functionalized using a preformed, ready-to-use nitrilotriacetic acid-divalent metal cation (NTA-M2+) complex and polyethylene glycol (PEG) molecules. As a proof-of-concept, we demonstrate the oriented immobilization of a recombinant cadherin fragment engineered with a hexahistidine tag (6His-tag) onto the MNPs. Our developed methodology is simple and direct, enabling the oriented bioconjugation of His-tagged cadherins to MNPs while preserving protein functionality and the colloidal stability of the MNPs, and could be extended to other proteins expressing a polyhistidine tag. When compared to the traditional method where NTA is first conjugated to the MNPs and afterward free metal ions are added to form the complex, this novel strategy results in a higher functionalization efficiency while avoiding MNP aggregation. Additionally, our method allows for covalent bonding of the cadherin fragments to the MNP surface while preserving functionality, making it highly versatile. Finally, our strategy not only ensures the correct orientation of the protein fragments on the MNPs but also allows for the precise control of their density. This feature enables the selective targeting of E-cadherin-expressing cells only when MNPs are decorated with a high density of cadherin fragments.

The present invention relates to a process to carry out two or more enzymatic reactions in a reaction medium, wherein the process comprises providing a system comprising at least two substantially homogeneous and colloidal populations of magnetic nanoparticles (MNPs) and applying one or more external alternating magnetic field to produce the simultaneous or sequential activation of the enzymes functionalized on the surface of each population of MNPs so that the enzymatic reactions can be thermally activated.

[EN] The present invention relates to an in vitro method for detecting at least one target poly- nucleotide in a test sample, wherein the method comprises the steps of contacting the test sample with a first oligonucleotide and a second oligonucleotide and detecting the hybridization between the first and the second oligonucleotides to the at least one target polynucleotide. The present invention also relates to devices or systems to implement the method, and kits of parts comprising said oligonucleotides., [FR] La présente invention concerne un procédé in vitro pour détecter au moins un poly-nucléotide cible dans un échantillon de test, le procédé comprenant les étapes consistant à mettre en contact l'échantillon de test avec un premier oligonucléotide et un second oligonucléotide et à détecter l'hybridation entre le premier et le second oligonucléotides avec le au moins un polynucléotide cible. La présente invention concerne également des dispositifs ou systèmes permettant de mettre en œuvre le procédé, et des kits d'éléments comprenant lesdits oligonucléotides.

[EN] The present invention relates to a process to carry out two or more enzymatic reactions in a reaction medium, wherein the process comprises providing a system comprising at least two substantially homogeneous and colloidal populations of magnetic nanoparticles (MNPs) and applying one or more external alternating magnetic field to produce the simultaneous or sequential activation of the enzymes functionalized on the surface of each population of MNPs so that the enzymatic reactions can be thermally activated., [FR] La présente invention concerne un procédé pour effectuer deux ou plusieurs réactions enzymatiques dans un milieu réactionnel, le procédé comprenant la fourniture d'un système comprenant au moins deux populations sensiblement homogènes et colloïdales de nanoparticules magnétiques (MNPs) et l'application d'un ou plusieurs champs magnétiques alternatifs externes pour produire l'activation simultanée ou séquentielle des enzymes fonctionnalisées sur la surface de chaque population de MNPs de telle sorte que les réactions enzymatiques peuvent être activées thermiquement.

Uniform Nd3+-doped LuVO4 nanophosphors have been synthesized for the first time in literature by using a poliol-basedmethod at 120 C fromNd3+ and vanadate precursors. After optimizing the Nd doping level, these phosphors present intense luminescence in the near-infrared biological windows. The X-ray attenuation capacity of the optimum nanophosphor has been found to be higher than that of a commercial X-ray computed tomography contrast agent. After surface coating with polyacrylic acid, such nanoparticles present high colloidal stability in physiological pHmediumand high cell viability. Because of these properties, the developedNd3+-doped LuVO4 nanoparticles have potential applications as a bimodal probe for NIR luminescent bioimaging and X-ray computed tomography.

The development of nanoplatforms prepared to perform both multimodal imaging and combined therapies in a single entity is a fast-growing field. These systems are able to improve diagnostic accuracy and therapy success. Multicomponent Nanoparticles (MCNPs), composed of iron oxide and gold, offer new opportunities for Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) diagnosis, as well as combined therapies based on Magnetic Hyperthermia (MH) and Photothermal Therapy (PT). In this work, we describe a new seed-assisted method for the synthesis of Au@Fe Nanoparticles (NPs) with a flower-like structure. For biomedical purposes, Au@Fe NPs were functionalized with a PEGylated ligand, leading to high colloidal stability. Moreover, the as-obtained Au@Fe-PEG NPs exhibited excellent features as both MRI and CT Contrast Agents (CAs), with high r2 relaxivity (60.5 mM−1⋅s−1) and X-ray attenuation properties (8.8 HU mM−1⋅HU). In addition, these nanoflowers presented considerable energy-to-heat conversion under both Alternating Magnetic Fields (AMFs) (∆T ≈ 2.5 °C) and Near-Infrared (NIR) light (∆T ≈ 17 °C). Finally, Au@Fe-PEG NPs exhibited very low cytotoxicity, confirming their potential for theranostics applications.

Figure S1, AC magnetic susceptibility characterization of different organs (tumor, liver, skin, and blood); Figure S2, scaled out-of-phase magnetic susceptibility of several tissues and nanoparticle standards scaled to their maximum to compare the location in temperature of the maxima.

Instrumentation, functionalization and characterization of MNPs, MNP stability assays, characterization of the click reactivity of the MNPs in suspension and on surfaces, metabolic glycoengineering, and MNP–cell interactions.

NMR spectrum of the POM-IL DOTMG-1; characterization of the DOTMG-1 PMMA films; cytotoxicity of the POM-IL DOTMG-1; and data from additional antibacterial assays.

[ES] El uso de nanotransportadores para la encapsulación de diferentes moléculas ha sido explorado a lo largo de los últimos años para múltiples aplicaciones. Ha sido utilizado por ejemplo para la vehiculización de moléculas hidrofóbicas en medios acuosos (y de hidrofílicas en medios oléicos), la protección de moléculas sensibles o la inmovilización de diferentes moléculas en soportes. Entre los diferentes tipos de nanotransportadores que han sido desarrollados, las nanocápsulas poliméricas han atraído la atención de multitud de investigadores debido a sus grandes ventajas. En esta tesis, nanoemulsiones recubiertas de polisacáridos han sido desarrolladas para su utilización como nanotransportadores de diferentes moléculas. Gracias a su versatilidad, estas nanocápsulas permiten la encapsulación de moléculas hidrofóbicas en el interior aceitoso, mientras que las moléculas hidrofílicas pueden ser atrapadas en la recubierta polimérica. Además, los componentes de las nanocápsulas pueden ser modificados a demanda de la aplicación final. Las nanocápsulas desarrolladas han demostrado ser muy efectivas para la encapsulación de antibióticos como bedaquilina y daptomicina para su uso en el tratamiento de infecciones causadas por Mycobacterium tuberculosis y Staphylococcus aureus resistente a la meticilina (SARM), respectivamente. Han sido utilizadas también en un estudio exploratorio para la encapsulación del fármaco disulfiram y su utilización alternativa en el tratamiento del cáncer de páncreas e infecciones causadas por SARM. También han mostrado gran capacidad como soportes para la inmovilización de la enzima cloroperoxidasa así como la encapsulación de partículas magnéticas. Por último, también han sido desarrolladas nanocápsulas para la encapsulación de nanopartículas de vanadato de holmio para su utilización como agentes de contraste. Todas las nanocápsulas desarrolladas han sido recubiertas con el polímero adecuado teniendo en cuenta la aplicación final y las necesidad, [EN] The use of nanocarriers for the encapsulation of different molecules has been explored over the recent years for multiple applications. They have been used for the vehiculization of hydrophobic molecules in aqueous media (or hydrophilic ones in oily media), protection of sensitive molecules or immobilization of different molecules in supports. Among the different nanocarriers that have been developed, polymeric nanocapsules have attracted the interest of many researchers thanks to their great advantages. In this thesis, polysaccharide coated nanoemulsions have been developed as potential nanocarriers for the encapsulation of different molecules. Thanks to their versatility, these nanocarriers allow the encapsulation of hydrophobic in the oily core, while hydrophilic ones can be entrapped in the polymer coating. Besides, the components of the nanocapsules can be modified upon the needs of the final application. All the developed nanocapsules were coated with the adequate polymer depending on the final application and the characteristics that needed to be achieved. Both chitosan, alginate and xanthan were used successfully. The developed nanocapsules have proven to be very effective for the encapsulation of antibiotics such as bedaquiline and daptomycin used the treatment of Mycobacterium tuberculosis and Methicillin-resistant Staphylococcus aureus (MRSA) infections, respectively. An exploratory research has been also carried out to encapsulate the drug disulfiram for its repurposing for the treatment of pancreatic cancer and MRSA infections. The developed nanocapsules have shown great capability as immobilizing agents of the enzyme chloroperoxidase and the encapsulation of magnetic nanoparticles (NP). They have also been able to encapsulate holmium vanadate NP for their use as contrast agents. Physicochemical characterization as well as efficacy test for the different purposes were performed in all the cases. For all the tested applications, the developed nanoca

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.

SARS-CoV-2, a positive-strand RNA virus has caused devastating effects. The standard method for COVID diagnosis is based on polymerase chain reaction (PCR). The method needs expensive reagents and equipment and well-trained personnel and takes a few hours to be completed. The search for faster solutions has led to the development of immunological assays based on antibodies that recognize the viral proteins that are faster and do not require any special equipment. Here, we explore an innovative analytical approach based on the sandwich oligonucleotide hybridization which can be adapted to several biosensing devices including thermal lateral flow and electrochemical devices, as well as fluorescent microarrays. Polypurine reverse-Hoogsteen hairpins (PPRHs) oligonucleotides that form high-affinity triplexes with the polypyrimidine target sequences are used for the efficient capture of the viral genome. Then, a second labeled oligonucleotide is used to detect the formation of a trimolecular complex in a similar way to antigen tests. The reached limit of detection is around 0.01 nM (a few femtomoles) without the use of any amplification steps. The triplex enhanced nucleic acid detection assay (TENADA) can be readily adapted for the detection of any pathogen requiring only the knowledge of the pathogen genome sequence.

Nanomedicine has been considered a promising tool for biomedical research and clinical practice in the 21st century because of the great impact nanomaterials could have on human health. The generation of new smart nanomaterials, which enable time- and space-controlled drug delivery, improve the limitations of conventional treatments, such as non-specific targeting, poor biodistribution and permeability. These smart nanomaterials can respond to internal biological stimuli (pH, enzyme expression and redox potential) and/or external stimuli (such as temperature, ultrasound, magnetic field and light) to further the precision of therapies. To this end, photonic and magnetic nanoparticles, such as gold, silver and iron oxide, have been used to increase sensitivity and responsiveness to external stimuli. In this review, we aim to report the main and most recent systems that involve photonic or magnetic nanomaterials for external stimulus-responsive drug release. The uniqueness of this review lies in highlighting the versatility of integrating these materials within different carriers. This leads to enhanced performance in terms of in vitro and in vivo efficacy, stability and toxicity. We also point out the current regulatory challenges for the translation of these systems from the bench to the bedside, as well as the yet unresolved matter regarding the standardization of these materials.

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.

[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.