Limbal Stem Cells on Bacterial Nanocellulose Carriers for Ocular Surface Regeneration.

Limbal stem cells (LSCs) are already used in cell-based treatments for ocular surface disorders. Clinical translation of LSCs-based therapies critically depends on the successful delivery, survival, and retention of these therapeutic cells to the desired region. Such a major bottleneck could be overcome by using an appropriate carrier to provide anchoring sites and structural support to LSC culture and transplantation. Bacterial nanocellulose (BNC) is an appealing, yet unexplored, candidate for this application because of its biocompatibility, animal-free origin and mechanical stability. Here, BNC as a vehicle for human embryonic stem cells-derived LSC (hESC-LSC) are investigated. To enhance cell-biomaterial interactions, a plasma activation followed by a Collagen IV and Laminin coating of the BNC substrates is implemented. This surface functionalization with human extracellular matrix proteins greatly improved the attachment and survival of hESC-LSC without compromising the flexible, robust and semi-transparent nature of the BNC. The surface characteristics of the BNC substrates are described and a preliminary ex vivo test in simulated transplantation scenarios is provided. Importantly, it is shown that hESC-LSC retain their self-renewal and stemness characteristics up to 21 days on BNC substrates. These results open the door for future research on hESC-LSC/BNC constructs to treat severe ocular surface pathologies.

[Elements influencing the election of Family and Community Medicine]. / Factores que influyen en la elección de la especialidad de Medicina Familiar y Comunitaria.

AIM: To analyze the perceptions, motives and reasons that influence the election of Family and Community Medicine (FCM) speciality, thus exploring possible proposals for change in the health system model and university training. DESIGN: Descriptive-interpretative qualitative research from a socio-constructivist perspective. EMPLACEMENT: Medical speciality training departments in the Metropolitan Area of Barcelona. PARTICIPANTS AND CONTEXT: 55 first year junior doctors belonging to the FCM Barcelona Ciutat ICS training department were contacted; 25 agreed to participate. They were segmented into two groups depending on if the choice of FCM had been their first option or not. Through snowball sampling 11 more junior doctors from other specialities were recruited. METHOD: Three focus groups were formed: (a) first choice FCM, (b) not first choice FCM and (c) other specialities. Semi-structured 2-h long interviews took place with each of the groups. Literal transcription and inductive codification with a first triangulation within each group and a second one between the three of them and thematic content analyses. RESULTS: The choice of speciality is lived as an academic milestone and is thought determining professional and personally. It is a complex weave of influencing elements but some of main factors were university training, health system model, professional prospects and the social appreciation of the speciality. Analyzing the relation between these elements puts light on a phenomena we have called "the discredit of Primary Care (PC)". CONCLUSION: The FCM specialty will not be attractive in a hospital-centric health and training system that does not bet on PC organizationally or economically.

Accurate iron quantification in colloids and nanocomposites by a simple UV-Vis protocol.

The selection and comparative study is reported of calibration curves to quantify iron by a simple UV-Vis protocol based on the formation of iron (III) chloride complexes. The reliability of each calibration curve was evaluated using statistical and analytical parameters. The robustness of each calibration curve using superparamagnetic iron oxide nanoparticles (SPIONs) of different sizes and surface functionalization is demonstrated . We have also evaluated the effect of the particle coating and estimated the minimum time to ensure the full oxidation of iron (II) to (III) in sample solutions. Results from UV-Vis are comparable with those obtained from ICP-OES and from other spectroscopic techniques to quantify the iron. We advocate the proposed protocol as a simple and non-expensive route to determine accurately the iron content in colloidal and nanocomposite iron-based materials. Graphical abstract.

Metal Nanoparticle Carbon Gel Composites in Environmental Water Sensing Applications.

The synthesis of organic-inorganic nanocomposites that can interact with different environmental pollutants and can be mass-produced are very promising materials for the fabrication of chemical sensor devices. Among them, metal (or metal oxide) nanoparticles doped conductive porous carbon composites can be readily applied to the production of electrochemical sensors and show enhanced sensitivity for the measurement of water pollutants, thanks to the abundant accessible and functional sites provided by the interconnected porosity and the metallic nanoparticles, respectively. In this personal account, an overview of several synthesis routes of porous carbon composites containing metallic nanoparticles is given, paying special attention to those based on sol-gel techniques. These are very powerful to synthesize hybrid porous materials that can be easily processed into powders and thin films, so that they can be implemented in electrode fabrication processes based on screen-printing and lithography techniques, respectively. We emphasize the sol-gel routes developed in our group for the synthesis of bismuth or gold nanoparticle doped porous carbon composites applied to fabricate electrochemical sensors that can be scaled down to produce miniaturized on-chip sensing devices for the sensitive detection of heavy metal pollutants in water. The trend towards the miniaturization of electrochemical sensors to be readily employed as analytical tools in environmental monitoring follow the market requirements of rapid and accurate on-site analysis, small sample consumption and waste production, as well as potential for continuous or semi-continuous in-situ determination of a wide variety of target analytes.

Free-standing three-dimensional hollow bacterial cellulose structures with controlled geometry via patterned superhydrophobic-hydrophilic surfaces.

Bacteria can produce cellulose, one of the most abundant biopolymer on earth, and emerge as an interesting candidate to fabricate advanced materials. Cellulose produced by Komagataeibacter Xylinus, a bacterial strain, is a pure water insoluble biopolymer, without hemicellulose or lignin. Bacterial cellulose (BC) exhibits a nanofibrous porous network microstructure with high strength, low density and high biocompatibility and it has been proposed as cell scaffold and wound healing material. The formation of three dimensional (3D) cellulose self-standing structures is not simple. It either involves complex multi-step synthetic procedures or uses chemical methods to dissolve cellulose and remold it. Here we present an in situ single-step method to produce self-standing 3D-BC structures with controllable wall thickness, size and geometry in a reproducible manner. Parameters such as hydrophobicity of the surfaces, volume of the inoculum and time of culture define the resulting 3D-BC structures. Hollow spheres and convex domes can be easily obtained by changing the surface wettability. The potential of these structures as a 3D cell scaffold is exemplified supporting the growth of mouse embryonic stem cells within a hollow spherical BC structure, indicating its biocompatibility and future prospective.

A Recoverable Ruthenium Aqua Complex Supported on Silica Particles: An Efficient Epoxidation Catalyst.

The preparation and characterization of complexes with a phosphonated terpyridine (trpy) ligand (trpy-P-Et) and a bidentate pyridylpyrazole (pypz-Me) ligand, with formula [RuII (trpy-P-Et)(pypz-Me)X]n+ (2: X=Cl, n=1; 3: X=H2 O, n=2), is described, together with the anchoring of 3 on two types of supports: mesoporous silica particles (SP) and silica-coated magnetic particles (MSP). Aqua complex 3 is easily obtained by heating 2 in refluxing water and exhibits a two-electron RuIV/II redox process. It was anchored on SP and MSP supports by two different synthetic strategies, yielding the heterogeneous systems SP@3 and MSP@3, which were fully characterized by IR and UV/Vis spectroscopy, SEM, cyclic voltammetry, and differential pulse voltammetry. Catalytic olefin epoxidation was tested with molecular complex 3 and its SP@3 and MSP@3 heterogeneous counterparts, including reuse of the heterogeneous systems. The MSP@3 material can be easily recovered by a magnet, which facilitates its reusability.

Magnetically Decorated Multi-Walled Carbon Nanotubes as Dual MRI and SPECT Contrast Agents.

Carbon nanotubes (CNTs) have been proposed as one of the most promising nanomaterials to be used in biomedicine for their applications in drug/gene delivery as well as biomedical imaging. The present study developed radio-labeled iron oxide decorated multi-walled CNTs (MWNT) as dual magnetic resonance (MR) and single photon emission computed tomography (SPECT) imaging agents. Hybrids containing different amounts of iron oxide were synthesized by in situ generation. Physicochemical characterisations revealed the presence of superparamagnetic iron oxide nanoparticles (SPION) granted the magnetic properties of the hybrids. Further comprehensive examinations including high resolution transmission electron microscopy (HRTEM), fast Fourier transform simulations (FFT), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) assured the conformation of prepared SPION as γ-Fe2O3. High r2 relaxivities were obtained in both phantom and in vivo MRI compared to the clinically approved SPION Endorem®. The hybrids were successfully radio-labeled with technetium-99m through a functionalized bisphosphonate and enabled SPECT/CT imaging and γ-scintigraphy to quantitatively analyze the biodistribution in mice. No abnormality was found by histological examination and the presence of SPION and MWNT were identified by Perls stain and Neutral Red stain, respectively. TEM images of liver and spleen tissues showed the co-localization of SPION and MWNT within the same intracellular vesicles, indicating the in vivo stability of the hybrids after intravenous injection. The results demonstrated the capability of the present SPION-MWNT hybrids as dual MRI and SPECT contrast agents for in vivo use.

In vitro angiogenic performance and in vivo brain targeting of magnetized endothelial progenitor cells for neurorepair therapies.

Endothelial progenitor cells (EPCs) represent a promising approach for cell-based therapies to induce tissue repair; however, their effective delivery into the brain has remained a challenge. We loaded EPCs with superparamagnetic iron oxide nanoparticles (SPIONs), assessed their angiogenic potential and evaluated their guidance to the brain using an external magnet. SPIONs were stored in the cytoplasm within endosomes/lysosomes as observed by transmission electron microscopy (TEM) and could be visualized as hypointense signals by magnetic resonance imaging (MRI) T2-weighted images. In vitro SPION-loaded EPCs were fully functional, forming vessel-like structures in Matrigel®, and displayed enhanced migration and secretion of growth factors (VEGF and FGF), which was associated with a moderate increase in reactive oxygen species production. Furthermore, in vivo MRI of treated mice showed accumulated hypointense signals consistent with SPION-loaded EPCs engraftment. Thus, we demonstrate that loading EPCs with SPIONs represents a safe and effective strategy for precise cell guidance into specific brain areas. FROM THE CLINICAL EDITOR: This study investigates the potential role of endothelial progenitor cells in neuro-repair strategies of the central nervous system using SPION-loaded EPCs and magnetic guidance to the target organ. The authors demonstrate ex vivo cellular viability and maintained function following SPION load as well as successful guidance of the EPCs to the target site via MR imaging in a murine model.

In situ shaping of intricated 3D bacterial cellulose constructs using sacrificial agarose and diverted oxygen inflow.

Bacterial cellulose (BC) is gathering increased attention due to its remarkable physico-chemical features. The high biocompatibility, hydrophilicity, and mechanical and thermal stability endorse BC as a suitable candidate for biomedical applications. Nonetheless, exploiting BC for tissue regeneration demands three-dimensional, intricately shaped implants, a highly ambitious endeavor. This challenge is addressed here by growing BC within a sacrificial viscoelastic medium consisting of an agarose gel cast inside polydimethylsiloxane (PDMS) molds imprinted with the features of the desired implant. BC produced with and without agarose has been compared through SEM, TGA, FTIR, and XRD, probing the mild impact of the agarose on the BC properties. As a first proof of concept, a PDMS mold shaped as a doll's ear was used to produce a BC perfect replica, even for the smallest features. The second trial comprised a doll face imprinted on a PDMS mold. In that case, the BC production included consecutive deactivation and activation of the aerial oxygen stream. The resulting BC face clone fitted perfectly and conformally with the template doll face, while its rheological properties were comparable to those of collagen. This streamlining concept conveys to the biosynthesized nanocelluloses broader opportunities for more advanced prosthetics and soft tissue engineering uses.

Photon upconversion crystals doped bacterial cellulose composite films as recyclable photonic bioplastics.

Biopolymers currently utilized as substitutes for synthetic polymers in photonics applications are predominantly confined to linear optical color responses. Herein we expand their applications in non-linear optics by integrating with triplet-triplet annihilation photon upconversion crystals. A photon upconverting biomaterial is prepared by cultivating Pd(II) meso-tetraphenyl tetrabenzoporphine: 9,10-diphenyl anthracene (sensitizer: annihilator) crystals on bacterial cellulose hydrogel that serves both as host and template for the crystallization of photon upconversion chromophores. Coating with gelatin improves the material's optical transparency by adjusting the refractive indices. The prepared material shows an upconversion of 633 nm red light to 443 nm blue light, indicated by quadratic to linear dependence on excitation power density (non-linearly). Notably, components of this material are physically dis-assembled to retrieve 66 ± 1% of annihilator, at the end of life. Whereas, the residual clean biomass is subjected to biodegradation, showcasing the sustainability of the developed photonics material.

Acceptability of multimodal and multidisciplinary group-based program for chronic low back pain: a qualitative study.

BACKGROUND: The Programa d'Atenció Integral pels Pacients amb Dolor Crònic (PAINDOC) is a multimodal and multidisciplinary group-based program that integrates pain neuroscience education, mindfulness meditation, pain psychotherapy, Empowered Relief, and therapeutic exercise. It serves as a therapeutic option for individuals with chronic low back pain, providing them with comprehensive adaptive strategies for pain management. OBJECTIVE: This qualitative study explores participants' retrospective acceptability of the PAINDOC Program. METHODS: To ensure demographic variability and information power, a purposive sampling approach was applied. Twelve participants were interviewed through three focus groups, supplemented with four individual semi-structured interviews. Data was analyzed using reflexive thematic analysis and evaluated based on the Therapeutic Framework of Acceptability. RESULTS: Participants provide positive feedback regarding active pain coping strategies and improved self-management. While certain aspects of the Program were more emphasized, participants integrated tools from all components. Strategies included pain reconceptualization, positive self-talk, or problem-solving. The Program's ethicality was closely linked to individual values and may also be influenced by time constraints of certain program elements, the immediate effects of specific approaches, participant perceptions, and individual preferences. CONCLUSIONS: The findings provide valuable insights into the acceptability of the PAINDOC Program, guiding future improvements and the development of similar interventions.

Multidisciplinary approaches to chronic pain management have been explored and are recognized as an effective way to address the complexity of chronic pain conditions. These approaches often involve the collaboration of healthcare professionals from various disciplines.Multimodal pain management programs typically combine various treatment modalities, including physical therapy, cognitive-behavioral therapy, medication, and exercise.Studies have shown that multidisciplinary and multimodal interventions can be effective in reducing pain intensity, improving physical function, and enhancing quality of life in chronic low back pain patients. What does this study add? The multidisciplinary and multimodal group-based PAINDOC Program is acceptable for chronic low back pain patients.Participants noted the effectiveness of the program in helping them adopt active pain coping strategies and improve self-management.The ethicality of the multimodal Program depends on individual personal value systems, as certain program components may be less suitable for some participants.There might be some barriers to program adherence, including limited available time, the higher physical demands of exercise, the immediate effects of certain approaches, participants' perceptions, and individual needs and preferences.

The European Polysaccharide Network of Excellence (EPNOE) research roadmap 2040: Advanced strategies for exploiting the vast potential of polysaccharides as renewable bioresources.

Polysaccharides are among the most abundant bioresources on earth and consequently need to play a pivotal role when addressing existential scientific challenges like climate change and the shift from fossil-based to sustainable biobased materials. The Research Roadmap 2040 of the European Polysaccharide Network of Excellence (EPNOE) provides an expert's view on how future research and development strategies need to evolve to fully exploit the vast potential of polysaccharides as renewable bioresources. It is addressed to academic researchers, companies, as well as policymakers and covers five strategic areas that are of great importance in the context of polysaccharide related research: (I) Materials & Engineering, (II) Food & Nutrition, (III) Biomedical Applications, (IV) Chemistry, Biology & Physics, and (V) Skills & Education. Each section summarizes the state of research, identifies challenges that are currently faced, project achievements and developments that are expected in the upcoming 20 years, and finally provides outlines on how future research activities need to evolve.

Drug use in patients with dementia: a register-based study in the health region of Girona (Catalonia/Spain).

PURPOSE: To describe the pattern of drug consumption among patients with dementia in a geographically defined general population in Catalonia (Spain), and to determine its association with age, gender, type of dementia and severity indicators. METHODS: Cross-sectional study that included 1,894 cases of dementia registered by the Registry of Dementias of Girona from 2007 to 2009. Prescribed drugs were categorized according to the Anatomical Therapeutic Chemical (ATC) classification. A descriptive analysis of drug consumption was stratified according to age, gender, dementia subtypes and dementia severity. Binary logistic regression models were adjusted to detect the association of these variables with drug consumption according to the ATC groups. RESULTS: The most commonly prescribed drugs were for the central nervous system (CNS) (96.4 %), cardiovascular system (79.4 %) and digestive and metabolic system categories (77.7 %). No significant differences were found between the use of nervous system drugs and age, gender, dementia subtypes or dementia severity. The use of alimentary tract and metabolism related drugs, as well as cardiovascular and blood system drugs, were positively correlated with age and secondary dementia. The prevalence of use of cardiovascular and musculoskeletal drugs was higher in women than in men (OR: 1.34; OR: 1.26 respectively). A negative association was found between the severity of dementia and the use of musculoskeletal drugs (OR: 0.71), while its use was significantly higher in the youngest patients (OR: 1.71). CONCLUSIONS: Almost all patients with dementia received a CNS drug, being at risk of inappropriate treatment. Treatment for comorbidities in patients with dementia should not be withheld on the basis of age or dementia severity, but rather on the benefit/risk ratio of its prescription. Further studies are needed to evaluate potentially inappropriate drug use and possible untreated conditions in this population.

Ce1-xZrxO2 nanoparticles in bacterial cellulose, bio-based composites with self-regenerating antioxidant capabilities.

Bacterial cellulose (BC) is an emerging biopolymer with ever-widening uses in the biomedical field due to its purity, mechanical stability, conformability, moisture control, and biocompatibility. In the wet form, its highly porous nanofibrillar structure and abundant surface hydroxyl groups enable the functionalisation of BC with inorganic nanoparticles (NPs), granting the material additional purposive capabilities. As oxidative stress caused by reactive oxygen species (ROS) negatively affects various cellular structures, the functionalisation of BC with CeO2 NPs, known antioxidants, is pursued in this work to achieve composites capable of minimising inflammation and tissue damage. We report on low-temperature in situ syntheses of CeO2 NPs in BC enabling the formation of BC-CeO2 composites that exhibit self-regenerating antioxidant properties, as verified by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays and studies of the evolution in the CeO2 absorption edge (indicative of the Ce3+ and Ce4+ fractions). X-Ray photoelectron spectroscopy (XPS) further reveals that incorporation of zirconium into the CeO2 lattice leads to a four-fold increase in the Ce3+: Ce4+ ratio, thereby enhancing the composite antioxidant performance as exemplified by BC-Ce0.6Zr0.4O2 recording the highest %DPPH scavenging per unit mass of NPs among the BC-Ce1-xZrxO2 studied systems.

Cell-Laden 3D Hydrogels of Type I Collagen Incorporating Bacterial Nanocellulose Fibers.

There is a growing interest in developing natural hydrogel-based scaffolds to culture cells in a three-dimensional (3D) millieu that better mimics the in vivo cells' microenvironment. A promising approach is to use hydrogels from animal tissues, such as decellularized extracellular matrices; however, they usually exhibit suboptimal mechanical properties compared to native tissue and their composition with hundreds of different protein complicates to elucidate which stimulus triggers cell's responses. As simpler scaffolds, type I collagen hydrogels are used to study cell behavior in mechanobiology even though they are also softer than native tissues. In this work, type I collagen is mixed with bacterial nanocellulose fibers (BCf) to develop reinforced scaffolds with mechanical properties suitable for 3D cell culture. BCf were produced from blended pellicles biosynthesized from Komagataeibacter xylinus. Then, BCf were mixed with concentrated collagen from rat-tail tendons to form composite hydrogels. Confocal laser scanning microscopy and scanning electron microscopy images confirmed the homogeneous macro- and microdistribution of both natural polymers. Porosity analysis confirmed that BCf do not disrupt the scaffold structure. Tensile strength and rheology measurements demonstrated the reinforcement action of BCf (43% increased stiffness) compared to the collagen hydrogel while maintaining the same viscoelastic response. Additionally, this reinforcement of collagen hydrogels with BCf offers the possibility to mix cells before gelation and then proceed to the culture of the 3D cell scaffolds. We obtained scaffolds with human bone marrow-derived mesenchymal stromal cells or human fibroblasts within the composite hydrogels, allowing a homogeneous 3D viable culture for at least 7 days. A smaller surface shrinkage in the reinforced hydrogels compared to type I collagen hydrogels confirmed the strengthening of the composite hydrogels. These collagen hydrogels reinforced with BCf might emerge as a promising platform for 3D in vitro organ modeling, tissue-engineering applications, and suitable to conduct fundamental mechanobiology studies.

Bioengineered extracellular vesicles: future of precision medicine for sepsis.

Sepsis is a syndromic response to infection and is frequently a final common pathway to death from many infectious diseases worldwide. The complexity and high heterogeneity of sepsis hinder the possibility to treat all patients with the same protocol, requiring personalized management. The versatility of extracellular vesicles (EVs) and their contribution to sepsis progression bring along promises for one-to-one tailoring sepsis treatment and diagnosis. In this article, we critically review the endogenous role of EVs in sepsis progression and how current advancements have improved EVs-based therapies toward their translational future clinical application, with innovative strategies to enhance EVs effect. More complex approaches, including hybrid and fully synthetic nanocarriers that mimic EVs, are also discussed. Several pre-clinical and clinical studies are examined through the review to offer a general outlook of the current and future perspectives of EV-based sepsis diagnosis and treatment.

Profile and variables related to antipsychotic consumption according to dementia subtypes.

BACKGROUND: Antipsychotics (APs) are usually prescribed to deal with behavioral and psychological symptoms of dementia (BPSD), but poor outcomes, important side effects, and high mortality risk should be addressed. The aim of this study was to estimate the prevalence of AP consumption in patients with dementia, and to describe and compare the sociodemographic and clinical characteristics of patients consuming APs. METHODS: This was a cross-sectional study using 1,894 cases of dementia registered from 2007 to 2009 by the Registry of Dementias of Girona (ReDeGi), which is a population-based passive surveillance system of dementia diagnoses. APs were categorized according to the anatomical therapeutic chemical (ATC) classification, and grouped as typical antipsychotics (TAPs) or atypical antipsychotics (AAPs). Binary logistic regression analyses were used to detect the predictors of AP use as well as the variables associated with TAP or AAP prescription. RESULTS: APs were used in 29.6% of the cases, with Parkinsonian syndromes (PSd) being the subtype of dementia with the highest AP prescription (50.6% of the patients with PSd). AAPs were mainly prescribed in all subtypes of dementia, except in vascular dementia (VaD) and PSd, where no preference in TAP or AAP use was found. Psychotic antecedents, dementia with Lewy bodies (DLB) diagnoses, cognitive impairment, and BPSD were AP use predictors. AAP use was related to higher severity of dementia. CONCLUSIONS: Despite their disputed benefit-risk ratios, APs are extensively used, off-label, to treat BPSD, and AAPs are more commonly prescribed than TAPs. AP consumption was frequent in DLB, and was related to dementia severity indicators.

Bioevaluation of magnetic mesoporous silica rods: cytotoxicity, cell uptake and biodistribution in zebrafish and rodents.

Mesoporous silica nanoparticles (MSN) characterized by large surface area, pore volume, tunable chemistry, and biocompatibility have been widely studied in nanomedicine as imaging and therapeutic carriers. Most of these studies focused on spherical particles. In contrast, mesoporous silica rods (MSR) that are more challenging to prepare have been less investigated in terms of toxicity, cellular uptake, or biodistribution. Interestingly, previous studies showed that silica rods penetrate fibrous tissues or mucus layers more efficiently than their spherical counterparts. Recently, we reported the synthesis of MSR with distinct aspect ratios and validated their use in multiple imaging modalities by loading the pores with maghemite nanocrystals and functionalizing the silica surface with green and red fluorophores. Herein, based on an initial hypothesis of high liver accumulation of the MSR and a future vision that they could be used for early diagnosis or therapy in fibrotic liver diseases; the cytotoxicity and cellular uptake of MSR were assessed in zebrafish liver (ZFL) cells and the in vivo safety and biodistribution was investigated via fluorescence molecular imaging (FMI) and magnetic resonance imaging (MRI) employing zebrafish larvae and rodents. The selection of these animal models was prompted by the well-established fatty diet protocols inducing fibrotic liver in zebrafish or rodents that serve to investigate highly prevalent liver conditions such as non-alcoholic fatty liver disease (NAFLD). Our study demonstrated that magnetic MSR do not cause cytotoxicity in ZFL cells regardless of the rods' length and surface charge (for concentrations up to 50 µg ml-1, 6 h) and that MSR are taken up by the ZFL cells in large amounts despite their length of ∼1 µm. In zebrafish larvae, it was observed that they could be safely exposed to high MSR concentrations (up to 1 mg ml-1 for 96 h) and that the rods pass through the liver without causing toxicity. The high accumulation of MSR in rodents' livers at short post-injection times (20% of the administered dose) was confirmed by both FMI and MRI, highlighting the utility of the MSR for liver imaging by both techniques. Our results could open new avenues for the use of rod-shaped silica particles in the diagnosis of pathological liver conditions.

Fluorescent PLGA Nanocarriers for Pulmonary Administration: Influence of the Surface Charge.

Nearly four million yearly deaths can be attributed to respiratory diseases, prompting a huge worldwide health emergency. Additionally, the COVID-19 pandemic's death toll has surpassed six million, significantly increasing respiratory disease morbidity and mortality rates. Despite recent advances, it is still challenging for many drugs to be homogeneously distributed throughout the lungs, and specifically to reach the lower respiratory tract with an accurate sustained dose and minimal systemic side effects. Engineered nanocarriers can provide increased therapeutic efficacy while lessening potential biochemical adverse reactions. Poly(lactic-co-glycolic acid) (PLGA), a biodegradable polymer, has attracted significant interest as an inhalable drug delivery system. However, the influence of the nanocarrier surface charge and its intratracheal instillation has not been addressed so far. In this study, we fabricated red fluorescent PLGA nanocapsules (NCs)-Cy5/PLGA-with either positive (Cy5/PLGA+) or negative surface charge (Cy5/PLGA-). We report here on their excellent colloidal stability in culture and biological media, and after cryo-storage. Their lack of cytotoxicity in two relevant lung cell types, even for concentrations as high as 10 mg/mL, is also reported. More importantly, differences in the NCs' cell uptake rates and internalization capacity were identified. The uptake of the anionic system was faster and in much higher amounts-10-fold and 2.5-fold in macrophages and epithelial alveolar cells, respectively. The in vivo study demonstrated that anionic PLGA NCs were retained in all lung lobules after 1 h of being intratracheally instilled, and were found to accumulate in lung macrophages after 24 h, making those nanocarriers especially suitable as a pulmonary immunomodulatory delivery system with a marked translational character.

Magnetic Mesoporous Silica Nanorods Loaded with Ceria and Functionalized with Fluorophores for Multimodal Imaging.

Multifunctional magnetic nanocomposites based on mesoporous silica have a wide range of potential applications in catalysis, biomedicine, or sensing. Such particles combine responsiveness to external magnetic fields with other functionalities endowed by the agents loaded inside the pores or conjugated to the particle surface. Different applications might benefit from specific particle morphologies. In the case of biomedical applications, mesoporous silica nanospheres have been extensively studied while nanorods, with a more challenging preparation, have attracted much less attention despite the positive impact on the therapeutic performance shown by seminal studies. Here, we report on a sol-gel synthesis of mesoporous rodlike silica particles of two distinct lengths (1.4 and 0.9 µm) and aspect ratios (4.7 and 2.2) using Pluronic P123 as a structure-directing template and rendering ∼1 g of rods per batch. Iron oxide nanoparticles have been synthesized within the pores yielding maghemite (γ-Fe2O3) nanocrystals of elongated shape (∼7 nm × 5 nm) with a [110] preferential orientation along the rod axis and a superparamagnetic character. The performance of the rods as T2-weighted MRI contrast agents has also been confirmed. In a subsequent step, the mesoporous silica rods were loaded with a cerium compound and their surface was functionalized with fluorophores (fluorescamine and Cyanine5) emitting at λ = 525 and 730 nm, respectively, thus highlighting the possibility of multiple imaging modalities. The biocompatibility of the rods was evaluated in vitro in a zebrafish (Danio rerio) liver cell line (ZFL), with results showing that neither long nor short rods with magnetic particles caused cytotoxicity in ZFL cells for concentrations up to 50 µg/ml. We advocate that such nanocomposites can find applications in medical imaging and therapy, where the influence of shape on performance can be also assessed.