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Mortality rates among pluripathological patients are significantly higher in the hospital setting, with advanced age and dependence on certain vital functions the main clinical aspects. Other features involved in the care, such as the loss of autonomy and social problems, have important ethical implications. The aim of this article is to analyze the health problems and the functional and social situation of chronic patients after hospital admission in order to determine their care needs and the ethical implications these might have. For this, a cross-sectional descriptive study is being carried out with a sample of 111 chronic pluripathological patients admitted to the internal medicine service and discharged later. Overall, 96.6% of the patients in the sample were dependent, 91.7% had social problems or were at social risk and 36.9% had cognitive impairment. Among dependent patients, 59.4% had social problems (p = 0.029), 19.2% lived alone (p = 0.13), and in 73.3% of cases the housing was inadequate (p = 0.47). Among those with cognitive impairment, 79.5% of patients had social problems (p = 0.001), and 10.3% lived alone (p = 0.038). The results of the study confirm the presence of dependence and social problems at hospital discharge in a high proportion of chronic patients. Planning their care can lead to ethical conflicts related to the use of information technologies, which are destined to promote the patients’ autonomy, and to the social problems associated with the illness.

We have prepared different polymeric chiral bifunctional thioureas and squaramides by modification of the very well-known polymers of intrinsic microporosity (PIM), specifically PIM-1 and PIM-CO-1, to be used as recoverable organocatalysts. The installation of the chiral structures into the polymers has been done in two or three steps in high yields. The catalytic activity of the resulting materials has been proved in the stereoselective nitro-Michael addition and in a cascade process, which allows the synthesis of enantioenriched 4H-chromene derivatives. Squaramide II and thiourea III have been used in six cycles maintaining their activity.

Antimicrobial Photodynamic Therapy (aPDT) is an innovative and promising method for combating infections, reducing the risk of antimicrobial resistance compared to traditional antibiotics. Squaraine (SQ) dyes can be considered promising photosensitizers (PSs) but are generally hydrophobic molecules that can self-aggregate under physiological conditions. To overcome these drawbacks, a possible solution is to incorporate SQs inside nanoparticles (NPs). The present work deals with the design and development of innovative nanophotosensitizers based on poly lactic-co-glycolic acid (PLGA) NPs incorporating a brominated squaraine (BrSQ) with potential application in aPDT. Two designs of experiments (DoEs) based on the single emulsion and nanoprecipitation methods were set up to investigate how different variables (type of solvent, solvent ratio, concentration of PLGA, stabilizer and dye, sonication power and time) can affect the size, zeta (ζ)-potential, yield, entrapment efficiency, and drug loading capacity of the SQ-PLGA NPs. SQ-PLGA NPs were characterized by NTA, FE-SEM, and UV-Vis spectroscopy and the ability to produce reactive oxygen species (ROS) was evaluated, proving that ROS generation ability is preserved in SQ-PLGA. In vitro antimicrobial activity against Gram-positive bacteria in planktonic state using Staphylococcus aureus was conducted in different conditions and pH to evaluate the potential of these nanophotosensitizers for aPDT in the local treatment of infections.

Mesoporous bioactive glasses (MBGs) of the SiO2–CaO–P2O5 system are biocompatible materials with a quick and effective in vitro and in vivo bioactive response. MBGs can be enhanced by including therapeutically active ions in their composition, by hosting osteogenic molecules within their mesopores, or by decorating their surfaces with mesenchymal stem cells (MSCs). In previous studies, our group showed that MBGs, ZnO-enriched and loaded with the osteogenic peptide osteostatin (OST), and MSCs exhibited osteogenic features under in vitro conditions. The aim of the present study was to evaluate bone repair capability after large bone defect treatment in distal femur osteoporotic rabbits using MBGs (76%SiO2–15%CaO–5%P2O5–4%ZnO (mol-%)) before and after loading with OST and MSCs from a donor rabbit. MSCs presence and/or OST in scaffolds significantly improved bone repair capacity at 6 and 12 weeks, as confirmed by variations observed in trabecular and cortical bone parameters obtained by micro-CT as well as histological analysis results. A greater effect was observed when OST and MSCs were combined. These findings may indicate the great potential for treating critical bone defects by combining MBGs with MSCs and osteogenic peptides such as OST, with good prospects for translation to clinical practice.

The increasing interest in innovative solutions for addressing bone defects has driven research into the use of Bioactive Mesoporous Glasses (MBGs). These materials, distinguished by their well-ordered mesoporous structure, possess the capability to accommodate plant extracts with well-established osteogenic properties, including bovine lactoferrin (bLF), as part of their 3D scaffold composition. This harmonizes seamlessly with the ongoing advancements in the field of biomedicine. In this study, we fabricated 3D scaffolds utilizing MBGs loaded with extracts from parsley leaves (PL) and embryogenic cultures (EC), rich in bioactive compounds such as apigenin and kaempferol, which hold potential benefits for bone metabolism. Gelatin Methacryloyl (GelMa) served as the polymer, and bLF was included in the formulation. Cytocompatibility, Runx2 gene expression, ALP enzyme activity, and biomineralization were assessed in preosteoblastic MC3T3-E1 cell cultures. MBGs effectively integrated PL and EC extracts with loadings between 22.6 ± 0.1 and 43.6 ± 0.3 µM for PL and 26.3 ± 0.3 and 46.8 ± 0.4 µM for EC, ensuring cell viability through a release percentage between 28.3% and 59.9%. The incorporation of bLF in the 3D scaffold formulation showed significant differences compared to the control in all assays, even at concentrations below 0.2 µM. Combinations, especially PL + bLF at 0.19 µM, demonstrated additive potential, with superior biomineralization compared to EC. In summary, this study highlights the effectiveness of MBGs in incorporating PL and EC extracts, along with bLF, into 3D scaffolds. The results underscore cytocompatibility, osteogenic activity, and biomineralization, offering exciting potential for future in vivo applications.

Bioactive mesoporous glass nanospheres (nanoMBGs) charged with antiosteoporotic drugs have great potential for the treatment of osteoporosis and fracture prevention. In this scenario, cells of the immune system are essential both in the development of disease and in their potential to stimulate therapeutic effects. In the present work, we hypothesize that nanoMBGs loaded with ipriflavone can exert a positive osteoimmune effect. With this objective, we assessed the effects of non-loaded and ipriflavone-loaded nanoparticles (nanoMBGs and nanoMBG-IPs, respectively) on CD4+ Th2 lymphocytes because this kind of cell is implicated in the inhibition of osseous loss by reducing the RANKL/OPG relationship through the secretion of cytokines. The results indicate that nanoMBGs enter efficiently in CD4+ Th2 lymphocytes, mainly through phagocytosis and clathrin-dependent mechanisms, without affecting the function of these T cells or inducing inflammatory mediators or oxidative stress, thus maintaining the reparative Th2 phenotype. Furthermore, the incorporation of the anti-osteoporotic drug ipriflavone reduces the potential unwanted inflammatory response by decreasing the presence of ROS and stimulating intracellular anti-inflammatory cytokine release like IL-4. These results evidenced that nanoMBG loaded with ipriflavone exerts a positive osteoimmune effect.

Vaccines represent one of the most significant advancements in public health since they prevented morbidity and mortality in millions of people every year. Conventionally, vaccine technology focused on either live attenuated or inactivated vaccines. However, the application of nanotechnology to vaccine development revolutionized the field. Nanoparticles emerged in both academia and the pharmaceutical industry as promising vectors to develop future vaccines. Regardless of the striking development of nanoparticles vaccines research and the variety of conceptually and structurally different formulations proposed, only a few of them advanced to clinical investigation and usage in the clinic so far. This review covered some of the most important developments of nanotechnology applied to vaccine technologies in the last few years, focusing on the successful race for the preparation of lipid nanoparticles employed in the successful anti-SARS-CoV-2 vaccines.

The production of customized polymeric hydrogels in the form of 3D scaffolds with application in bone tissue engineering is currently a topic of great interest. Based on gelatin methacryloyl (GelMa) as one of the most popular used biomaterials, GelMa with two different methacryloylation degrees (DM) was obtained, to achieve crosslinked polymer networks by photoinitiated radical polymerization. In this work, we present the obtention of new 3D foamed scaffolds based on ternary copolymers of GelMa with vinylpyrrolidone (VP) and 2-hydroxyethylmethacrylate (HEMA). All biopolymers obtained in this work were characterized by infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA), whose results confirm the presence of all copolymers in the crosslinked biomaterial. In addition, scanning electron microscopy (SEM) pictures were obtained verifying the presence of the porosity created by freeze-drying process. In addition, the variation in its swelling degree and its enzymatic degradation in vitro was analyzed as a function of the different copolymers obtained. This has allowed us to observe good control of the variation in these properties described above in a simple way by varying the composition of the different comonomers used. Finally, with these concepts in mind, biopolymers obtained were tested through assessment of several biological parameters such as cell viability and differentiation with MC3T3-E1 pre-osteoblastic cell line. Results obtained show that these biopolymers maintain good results in terms of cell viability and differentiation, along with tunable properties in terms of hydrophilic character, mechanical properties and enzymatic degradation.

Osteoporosis is the most common type of bone disease. Conventional treatments are based on the use of antiresorptive drugs and/or anabolic agents. However, these treatments have certain limitations, such as a lack of bioavailability or toxicity in non-specific tissues. In this regard, pleiotrophin (PTN) is a protein with potent mitogenic, angiogenic, and chemotactic activity, with implications in tissue repair. On the other hand, mesoporous silica nanoparticles (MSNs) have proven to be an effective inorganic drug-delivery system for biomedical applications. In addition, the surface anchoring of cationic polymers, such as polyethylenimine (PEI), allows for greater cell internalization, increasing treatment efficacy. In order to load and release the PTN to improve its effectiveness, MSNs were successfully internalized in MC3T3-E1 mouse pre-osteoblastic cells and human mesenchymal stem cells. PTN-loaded MSNs significantly increased the viability, mineralization, and gene expression of alkaline phosphatase and Runx2 in comparison with the PTN alone in both cell lines, evidencing its positive effect on osteogenesis and osteoblast differentiation. This proof of concept demonstrates that MSN can take up and release PTN, developing a potent osteogenic and differentiating action in vitro in the absence of an osteogenic differentiation-promoting medium, presenting itself as a possible treatment to improve bone-regeneration and osteoporosis scenarios.

In recent years, the functionalization of mesoporous silica nanoparticles (MSNs) with different types of responsive pore gatekeepers have shown great potential for the formulation of drug delivery systems (DDS) with minimal premature leakage and site-specific controlled release. New nanotechnological approaches have been developed with the objective of utilizing natural biopolymers as smart materials in drug delivery applications. Natural biopolymers are sensitive to various physicochemical and biological stimuli and are endowed with intrinsic biodegradability, biocompatibility, and low immunogenicity. Their use as biocompatible smart coatings has extensively been investigated in the last few years. This review summarizes the MSNs coating procedures with natural polysaccharides and protein-based biopolymers, focusing on their application as responsive materials to endogenous stimuli. Biopolymer-coated MSNs, which conjugate the nanocarrier features of mesoporous silica with the biocompatibility and controlled delivery provided by natural coatings, have shown promising therapeutic outcomes and the potential to emerge as valuable candidates for the selective treatment of various diseases.

Bone diseases are a global public concern that affect millions of people. Even though current treatments present high efficacy, they also show several side effects. In this sense, the development of biocompatible nanoparticles and macroscopic scaffolds has been shown to improve bone regeneration while diminishing side effects. In this review, we present a new trend in these materials, reporting several examples of materials that specifically recognize several agents of the bone microenvironment. Briefly, we provide a subtle introduction to the bone microenvironment. Then, the different targeting agents are exposed. Afterward, several examples of nanoparticles and scaffolds modified with these agents are shown. Finally, we provide some future perspectives and conclusions. Overall, this topic presents high potential to create promising translational strategies for the treatment of bone-related diseases. We expect this review to provide a comprehensive description of the incipient state-of-the-art of bone-targeting agents in bone regeneration.

Surface microbial colonization and its potential biofilm formation are currently a major unsolved problem, causing almost 75% of human infectious diseases. Pathogenic biofilms are capable of surviving high antibiotic doses, resulting in inefficient treatments and, subsequently, raised infection prevalence rates. Antibacterial coatings have become a promising strategy against the biofilm formation in biomedical devices due to their biocidal activity without compromising the bulk material. Here, we propose for the first time a silver-based metal–organic framework (MOF; here denoted AgBDC) showing original antifouling properties able to suppress not only the initial bacterial adhesion, but also the potential surface contamination. Firstly, the AgBDC stability (colloidal, structural and chemical) was confirmed under bacteria culture conditions by using agar diffusion and colony counting assays, evidencing its biocide effect against the challenging E. coli, one of the main representative indicators of Gram-negative resistance bacteria. Then, this material was shaped as homogeneous spin-coated AgBDC thin film, investigating its antifouling and biocide features using a combination of complementary procedures such as colony counting, optical density or confocal scanning microscopy, which allowed to visualize for the first time the biofilm impact generated by MOFs via a specific fluorochrome, calcofluor.

Nowadays, mesoporous bioactive glasses (MBGs) are envisaged as promising candidates in the field of bioceramics for bone tissue regeneration. This is ascribed to their singular chemical composition, structural and textural properties and easy-to-functionalize surface, giving rise to accelerated bioactive responses and capacity for local drug delivery. Since their discovery at the beginning of the 21st century, pioneering research efforts focused on the design and fabrication of MBGs with optimal compositional, textural and structural properties to elicit superior bioactive behavior. The current trends conceive MBGs as multitherapy systems for the treatment of bone-related pathologies, emphasizing the need of fine-tuning surface functionalization. Herein, we focus on the recent developments in MBGs for biomedical applications. First, the role of MBGs in the design and fabrication of three-dimensional scaffolds that fulfil the highly demanding requirements for bone tissue engineering is outlined. The different approaches for developing multifunctional MBGs are overviewed, including the incorporation of therapeutic ions in the glass composition and the surface functionalization with zwitterionic moieties to prevent bacterial adhesion. The bourgeoning scientific literature on MBGs as local delivery systems of diverse therapeutic cargoes (osteogenic/antiosteoporotic, angiogenic, antibacterial, anti-inflammatory and antitumor agents) is addressed. Finally, the current challenges and future directions for the clinical translation of MBGs are discussed.

Zinc-enriched mesoporous bioactive glasses (MBGs) are bioceramics with potential antibacterial and osteogenic properties. However, few assays have been performed to study these properties in animal models. In this study, MBGs enriched with up to 5% ZnO were synthesized, physicochemically characterized, and evaluated for their osteogenic activity both in vitro and in vivo. The ZnO MBGs showed excellent textural properties despite ZnO incorporation. However, the release of Zn2+ ions inhibited the mineralization process when immersed in simulated body fluid. In vitro assays showed significantly higher values of viability and expression of early markers of cell differentiation and angiogenesis in a ZnO-content-dependent manner. The next step was to study the osteogenic potential in a sheep bone defect model. Despite their excellent textural properties and cellular response in vitro, the ZnO MBGs were not able to integrate into the bone tissue, which can be explained in terms of inhibition of the mineralization process caused by Zn2+ ions. This work highlights the need to develop nanostructured materials for bone regeneration that can mineralize to interact with bone tissue and induce the processes of implant acceptance, cell colonization by osteogenic cells, and regeneration of lost bone tissue.

In this study, new blends of PCL/PEC have been prepared in an easy manner by casting with the objective of obtaining new biomaterials to apply to tissue engineering and bone regeneration. The PCL/PEC blends obtained, together with neat polymer blends, were characterized by infrared spectroscopy (FTIR), atomic force microscopy (AFM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). This full characterization is the key to disentangle the miscibility, which means good compatibility, of the polymer blends used in this work. The addition of increasing amounts of PEC, has shown in the new biomaterials obtained, a remarkable improvement in relation with the mechanical properties (manageable materials) and above all, in terms of an increase in their hydrophilic character with respect to the PCL neat polymer. The improvement of all these properties is reflected in their biological properties. With these thoughts in mind, the blends obtained were tested through the assessment of several biological parameters such as cell viability, proliferation, and differentiation of both the MC3T3-E1 osteoblastic cell line and hMSCs to evaluate their cell response to different polymer membranes aimed at bone tissue regeneration. “In vitro” biocompatibility methods have been chosen rather than in vivo studies due to their lower cost, faster procedure time, and minimum ethical concerns, and because it was the first time that the biological effects of these blends were studied. The results show that the PCL/PEC blends obtained, with tunable properties in terms of hydrophilic character and hydrolytic degradation, may be regarded as good candidates to perform “in vivo” tests and check their real-life applicability for bone regeneration. The polymer acronym (the weight percentage in the sub index) is PCLx/PECy as noted in table one with the summary of compositions.

Nanomedicines have revolutionized the treatment of certain types of cancer, as is the case of doxil, liposomal formulation with doxorubicin encapsulated, in the treatment of certain types of ovarian cancer, AIDS-related Kaposi sarcoma, and multiple myeloma. These nanomedicines can improve the performance of conventional chemotherapeutic treatments, with fewer side effects and better efficiency against cancer. Although liposomes have been used in some formulations, different nanocarriers with better features in terms of stability and adsorption capabilities are being explored. Among the available nanoparticles in the field, mesoporous silica nanoparticles (MSNP) have attracted great attention as drug delivery platforms for the treatment of different diseases. Here, a novel formulation based on MSNP loaded with a potent antitumor prodrug that works in vitro as well as in a clinically evaluated liposomal formulation has been developed. This novel formulation shows excellent prodrug encapsulation efficiency and effective release of the anticancer drug only under certain stimuli typical of tumor environments. This behavior is of capital importance for translating this nanocarrier to the clinic in the near future.

The Special Issue of Nanomaterials “Nanoparticles for Biomedical Applications” highlights the use of different types of nanoparticles for biomedical applications, including magnetic nanoparticles, mesoporous carbon nanoparticles, mesoporous bioactive glass nanoparticles, and mesoporous silica nanoparticles [...]

In search of new approaches to treat bone infection and prevent drug resistance development, a nanosystem based on hollow bioactive glass nanoparticles (HBGN) of composition 79.5SiO2-(18-x)CaO-2.5P2O5-xCuO (x = 0, 2.5 or 5 mol-% CuO) was developed. The objective of the study was to evaluate the capacity of the HBGN to be used as a nanocarrier of the broad-spectrum antibiotic danofloxacin and source of bactericidal Cu2+ ions. Core-shell nanoparticles with specific surface areas close to 800 m2/g and pore volumes around 1 cm3/g were obtained by using hexadecyltrimethylammonium bromide (CTAB) and poly(styrene)-block-poly(acrylic acid) (PS-b-PAA) as structure-directing agents. Flow cytometry studies showed the cytocompatibility of the nanoparticles in MC3T3-E1 pre-osteoblastic cell cultures. Ion release studies confirmed the release of non-cytotoxic concentrations of Cu2+ ions within the therapeutic range. Moreover, it was shown that the inclusion of copper in the system resulted in a more gradual release of danofloxacin that was extended over one week. The bactericidal activity of the nanosystem was evaluated with E. coli and S. aureus strains. Nanoparticles with copper were not able to reduce bacterial viability by themselves and Cu-free HBGN failed to reduce bacterial growth, despite releasing higher antibiotic concentrations. However, HBGN enriched with copper and danofloxacin drastically reduced bacterial growth in sessile, planktonic and biofilm states, which was attributed to a synergistic effect between the action of Cu2+ ions and danofloxacin. Therefore, the nanosystem here investigated is a promising candidate as an alternative for the local treatment of bone infections.

Background: We aimed to evaluate personality traits in patients with post-COVID syndrome, as well as the association with neuropsychiatric symptoms present in this disorder. Methods: The Big Five Structure Inventory was administered to 93 consecutive patients with a diagnosis of post-COVID syndrome as defined by the WHO and to demographically matched controls. We also performed a comprehensive evaluation of depression, anxiety, fatigue, sleep quality, cognitive function, and olfactory function. Results: Patients with post-COVID syndrome scored lower for emotional stability, equanimity, positive mood, and self-control. Extraversion, emotional stability, and openness correlated negatively with anxiety and depression levels. Conscientiousness correlated negatively with anxiety. No statistically significant correlations were observed between personality traits and cognitive function, sleep quality, olfactory function, or fatigue. Personality scores explained 36.3% and 41% of the variance in scores on the anxiety and depression scales, respectively. Two personality profiles with lower levels of emotional stability were associated with depression and anxiety. Conclusions: Our study shows higher levels of neuroticism in patients with post-COVID syndrome. Personality traits were predictive of the presence of depression and anxiety, but not cognitive function, sleep quality, or fatigue, in the context of post-COVID syndrome. These findings may have implications for the detection of patients at risk of depression and anxiety in post-COVID syndrome, and for the development of preventive and therapeutic interventions.

Nowadays, there is an ever-increasing interest in the development of systems able to guide and influence cell activities for bone regeneration. In this context, we have explored for the first time the combination of type-I collagen and superparamagnetic iron oxide nanoparticles (SPIONs) to design magnetic and biocompatible electrospun scaffolds. For this purpose, SPIONs with a size of 12 nm were obtained by thermal decomposition and transferred to an aqueous medium via ligand exchange with dimercaptosuccinic acid (DMSA). The SPIONs were subsequently incorporated into type-I collagen solutions to prove the processability of the resulting hybrid formulation by means of electrospinning. The optimized method led to the fabrication of nanostructured scaffolds composed of randomly oriented collagen fibers ranging between 100 and 200 nm, where SPIONs resulted distributed and embedded into the collagen fibers. The SPIONs-containing electrospun structures proved to preserve the magnetic properties of the nanoparticles alone, making these matrices excellent candidates to explore the magnetic stimuli for biomedical applications. Furthermore, the biological assessment of these collagen scaffolds confirmed high viability, adhesion, and proliferation of both pre-osteoblastic MC3T3-E1 cells and human bone marrow-derived mesenchymal stem cells (hBM-MSCs).

Currently, the design of nanomaterials for the treatment of different pathologies is presenting a major impact on biomedical research. Thanks to this, nanoparticles represent a successful strategy for the delivery of high amounts of drugs for the treatment of cancer. Different nanosystems have been designed to combat this pathology. However, the poor penetration of these nanomaterials into the tumor tissue prevents the drug from entering the inner regions of the tumor. Some bacterial strains have self-propulsion and guiding capacity thanks to their flagella. They also have a preference to accumulate in certain tumor regions due to the presence of different chemo-attractants factors. Bioconjugation reactions allow the binding of nanoparticles in living systems, such as cells or bacteria, in a simple way. Therefore, bacteria are being used as a transport vehicle for nanoparticles, facilitating their penetration and the subsequent release of the drug inside the tumor. This review would summarize the literature on the anchoring methods of diverse nanosystems in bacteria and, interestingly, their advantages and possible applications in cancer therapy.

(1) Background: Carbapenem-resistant Klesiella pneumoniae (CR-KP) infection rates depict an almost pre-antibiotic scenario since the pipeline for effective antibiotics against this pathogen has been almost entirely depleted. This study aims to evaluate the antibacterial effect of gold nanostars (GNS) alone or associated with some of the most widely used antibiotics for the treatment of CR-KP strains, i.e., meropenem or amikacin, on both planktonic and sessile forms. Additionally, we measured the effect of GNS on cell proliferation and biocompatibility in invertebrate in vivo models. (2) Materials and methods: GNS were made from gold seeds grown using a seeded-growth surfactant-free method assisted by silver ions and functionalized with mercapto-poly(ethylene glycol)amino by ligand exchange. The antimicrobial capacity, effect on cell proliferation, and biocompatibility of the most effective combination was evaluated in a Galleria mellonella model. (3) Results: The minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were 80 and 160 µM of GNS for all strains, respectively. The minimum biofilm inhibitory concentration (MBIC) and minimum biofilm eradication concentration (MBEC) were >320 µM of GNS for both. A synergy was found between GNS and amikacin. Larvae administered GNS plus amikacin were found to tolerate the treatment well, which prevented infection. (4) Conclusions: GNS are a promising anti-CR-KP nanomaterial.

A crucial challenge to face in the treatment of biofilm-associated infection is the ability of bacteria to develop resistance to traditional antimicrobial therapies based on the administration of antibiotics alone. This study aims to apply magnetic hyperthermia together with controlled antibiotic delivery from a unique magnetic-responsive nanocarrier for a combination therapy against biofilm. The design of the nanosystem is based on antibiotic-loaded mesoporous silica nanoparticles (MSNs) externally functionalized with a thermo-responsive polymer capping layer, and decorated in the outermost surface with superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs are able to generate heat upon application of an alternating magnetic field (AMF), reaching the temperature needed to induce a change in the polymer conformation from linear to globular, therefore triggering pore uncapping and the antibiotic cargo release. The microbiological assays indicated that exposure of E. coli biofilms to 200 µg/mL of the nanosystem and the application of an AMF (202 kHz, 30 mT) decreased the number of viable bacteria by 4 log10 units compared with the control. The results of the present study show that combined hyperthermia and antibiotic treatment is a promising approach for the effective management of biofilm-associated infections.

Prosthetic joint infection (PJI) is the second most common cause of arthroplasty failure. Though infrequent, it is one of the most devastating complications since it is associated with great personal cost for the patient and a high economic burden for health systems. Due to the high number of patients that will eventually receive a prosthesis, PJI incidence is increasing exponentially. As these infections are provoked by microorganisms, mainly bacteria, and as such can develop a biofilm, which is in turn resistant to both antibiotics and the immune system, prevention is the ideal approach. However, conventional preventative strategies seem to have reached their limit. Novel prevention strategies fall within two broad categories: (1) antibiotic- and (2) heavy metal-based surface modifications of titanium alloy prostheses. This review examines research on the most relevant titanium alloy surface modifications that use antibiotics to locally prevent primary PJI.

Mesoporous silica nanoparticles have been widely applied as carriers for cancer treatment. Among the different types of stimuli-responsive drug delivery systems, those sensitive to redox stimuli have attracted much attention. Their relevance arises from the high concentration of reductive species that are found within the cells, compared to bloodstream, which leads to the drug release taking place only inside cells. This review is intended to provide a comprehensive overview of the most recent trends in the design of redox-responsive mesoporous silica nanoparticles. First, a general description of the biological rationale of this stimulus is presented. Then, the different types of gatekeepers that are able to open the pore entrances only upon application of reductive conditions will be introduced. In this sense, we will distinguish among those targeted and those non-targeted toward cancer cells. Finally, a new family of bridged silica nanoparticles able to degrade their structure upon application of this type of stimulus will be presented.

Angiogenic biomaterials are designed to promote vascularization and tissue regeneration. Nanoparticles of bioactive materials loaded with drugs represent an interesting strategy to stimulate osteogenesis and angiogenesis and to inhibit bone resorption. In this work, porcine endothelial progenitor cells (EPCs), essential for blood vessel formation, were isolated and characterized to evaluate the in vitro effects of unloaded (NanoMBGs) and ipriflavone-loaded nanospheres (NanoMBG-IPs), which were designed to prevent osteoporosis. The expression of vascular endothelial growth factor receptor 2 (VEGFR2) was studied in EPCs under different culture conditions: (a) treatment with NanoMBGs or NanoMBG-IPs, (b) culture with media from basal, M1, and M2 macrophages previously treated with NanoMBGs or NanoMBG-IPs, (c) coculture with macrophages in the presence of NanoMBGs or NanoMBG-IPs, and (d) coculture with M2d angiogenic macrophages. The endocytic mechanisms for nanosphere incorporation by EPCs were identified using six different endocytosis inhibitors. The results evidence the great potential of these nanomaterials to enhance VEGFR2 expression and angiogenesis, after intracellular incorporation by EPCs through clathrin-dependent endocytosis, phagocytosis, and caveolae-mediated uptake. The treatment of EPCs with basal, M1, and M2 macrophage culture media and EPC/macrophage coculture studies also confirmed the angiogenic effect of these nanospheres on EPCs, even in the presence of phagocytic cells.

Peyronie and Dupuytren are pathologies characterized by the appearance of localized fibrotic lesions in an organ. These disorders originate from an excessive production of collagen in the tissue provoking dysfunction and functional limitations to the patients. Local administration of collagenase is the most used treatment for these fibrotic-type diseases, but a high lability of the enzyme limits its therapeutic efficacy. Herein, we present a novel methodology for the preparation of collagenase nanocapsules without affecting its enzymatic activity and capable of releasing the enzyme in response to an ultraviolet A (UVA) light stimulus. Polymeric coating around collagenase was formed by free-radical polymerization of acrylamide-type monomers. Their degradation capacity under UVA irradiation was provided by incorporating a novel photocleavable acrylamide-type crosslinker within the polymeric framework. This property allowed collagenase release to be triggered in a controlled manner by employing an easily focused stimulus. Additionally, UVA irradiation presents considerable benefits by itself due to its capacity to induce collagenase production in situ. An expected synergistic effect of collagenase nanocapsules in conjunction with UVA effect may present a promising treatment for these fibrotic diseases.

Upon contact with a biological milieu, nanomaterials tend to interact with biomolecules present in the media, especially proteins, leading to the formation of the so-called “protein corona”. As a result of these nanomaterial–protein interactions, the bio-identity of the nanomaterial is altered, which is translated into modifications of its behavior, fate, and pharmacological profile. For biomedical applications, it is fundamental to understand the biological behavior of nanomaterials prior to any clinical translation. For these reasons, during the last decade, numerous publications have been focused on the investigation of the protein corona of many different types of nanomaterials. Interestingly, it has been demonstrated that the structure of the protein corona can be divided into hard and soft corona, depending on the affinity of the proteins for the nanoparticle surface. In the present document, we explore the differences between these two protein coronas, review the analysis techniques used for their assessment, and reflect on their relevance for medical purposes.

Selenium nanoparticles (SeNPs) have been receiving special attention in recent years due to their antioxidant capacity and antitumor properties. However, the mechanisms associated with these properties remain to be elucidated. For this reason, a global transcriptome analysis has been designed in this work and it was carried out using human hepatocarcinoma cells and chitosan-stabilized SeNPs (Ch-SeNPs) to identify new targets and pathways related to the antitumor mechanisms associated with Ch-SeNPs. The results obtained confirm the alteration of the cell cycle and the effect of Ch-SeNPs on different tumor suppressors and other molecules involved in key mechanisms related to cancer progression. Furthermore, we demonstrated the antioxidant properties of these nanoparticles and their capacity to induce senescence, which was further confirmed through the measurement of β-galactosidase activity.

Combination therapies constitute a powerful tool for cancer treatment. By combining drugs with different mechanisms of action, the limitations of each individual agent can be overcome, while increasing therapeutic benefit. Here, we propose employing tumor-migrating decidua-derived mesenchymal stromal cells as therapeutic agents combining antiangiogenic therapy and chemotherapy. First, a plasmid encoding the antiangiogenic protein endostatin was transfected into these cells by nucleofection, confirming its expression by ELISA and its biological effect in an ex ovo chick embryo model. Second, doxorubicin-loaded mesoporous silica nanoparticles were introduced into the cells, which would act as vehicles for the drug being released. The effect of the drug was evaluated in a coculture in vitro model with mammary cancer cells. Third, the combination of endostatin transfection and doxorubicin-nanoparticle loading was carried out with the decidua mesenchymal stromal cells. This final cell platform was shown to retain its tumor-migration capacity in vitro, and the combined in vitro therapeutic efficacy was confirmed through a 3D spheroid coculture model using both cancer and endothelial cells. The results presented here show great potential for the development of combination therapies based on genetically-engineered cells that can simultaneously act as cellular vehicles for drug-loaded nanoparticles.

Infectious diseases hold third place in the top 10 causes of death worldwide and were responsible for more than 6.7 million deaths in 2016. Nanomedicine is a multidisciplinary field which is based on the application of nanotechnology for medical purposes and can be defined as the use of nanomaterials for diagnosis, monitoring, control, prevention, and treatment of diseases, including infectious diseases. One of the most used nanomaterials in nanomedicine are nanoparticles, particles with a nano-scale size that show highly tunable physical and optical properties, and the capacity to a wide library of compounds. This manuscript is intended to be a comprehensive review of the available recent literature on nanoparticles used for the prevention and treatment of human infectious diseases caused by different viruses, and bacteria from a clinical point of view by basing on original articles which talk about what has been made to date and excluding commercial products, but also by highlighting what has not been still made and some clinical concepts that must be considered for futures nanoparticles-based technologies applications.

In the search of a new biomaterial for the treatment of bone defects resulting from traumatic events, an osteoporosis scenario with bone fractures, tumor removal, congenital pathologies or implant revisions for infection, we developed 3D scaffolds based on mesoporous bioactive glasses (MBGs) (85 − x)SiO2–5P2O5–10CaO–xSrO (x = 0, 2.5 and 5 mol.%). The scaffolds with meso-macroporosity were fabricated by pouring a suspension of MBG powders in polyvinyl alcohol (PVA) into a negative template of polylactic acid (PLA), followed by removal of the template by extraction at low temperature. SrO-containing MBGs exhibited excellent properties for bone substitution including ordered mesoporous structure, high textural properties, quick in vitro bioactive response in simulated body fluid (SBF) and the ability of releasing concentrations of strontium ions able to stimulate expression of early markers of osteoblastic differentiation. Moreover, the direct contact of MC3T3-E1 pre-osteoblastic cells with the scaffolds confirmed the cytocompatibility of the three compositions investigated. Nevertheless, the scaffold containing 2.5% of SrO induced the best cellular proliferation showing the potential of this scaffold as a candidate to be further investigated in vitro and in vivo, aiming to be clinically used for bone regeneration applications in non-load bearing sites.

Current chemotherapy treatments lack great selectivity towards tumoral cells, which leads to nonspecific drug distribution and subsequent side effects. In this regard, the use of nanoparticles able to encapsulate and release therapeutic agents has attracted growing attention. In this sense, mesoporous silica nanoparticles (MSNs) have been widely employed as drug carriers owing to their exquisite physico-chemical properties. Because MSNs present a surface full of silanol groups, they can be easily functionalized to endow the nanoparticles with many different functionalities, including the introduction of moieties with affinity for the cell membrane or relevant compartments within the cell, thus increasing the efficacy of the treatments. This review manuscript will provide the state-of-the-art on MSNs functionalized for targeting subcellular compartments, focusing on the cytoplasm, the mitochondria, and the nucleus.

The incorporation and effects of hollow mesoporous nanospheres in the system SiO2–CaO (nanoMBGs) containing ipriflavone (IP), a synthetic isoflavone that prevents osteoporosis, were evaluated. Due to their superior porosity and capability to host drugs, these nanoparticles are designed as a potential alternative to conventional bioactive glasses for the treatment of periodontal defects. To identify the endocytic mechanisms by which these nanospheres are incorporated within the MC3T3-E1 cells, five inhibitors (cytochalasin B, cytochalasin D, chlorpromazine, genistein and wortmannin) were used before the addition of these nanoparticles labeled with fluorescein isothiocyanate (FITC–nanoMBGs). The results indicate that nanoMBGs enter the pre-osteoblasts mainly through clathrin-dependent mechanisms and in a lower proportion by macropinocytosis. The present study evidences the active incorporation of nanoMBG–IPs by MC3T3-E1 osteoprogenitor cells that stimulate their differentiation into mature osteoblast phenotype with increased alkaline phosphatase activity. The final aim of this study is to demonstrate the biocompatibility and osteogenic behavior of IP-loaded bioactive nanoparticles to be used for periodontal augmentation purposes and to shed light on internalization mechanisms that determine the incorporation of these nanoparticles into the cells.

The increasing emergence of new strains of Mycobacterium tuberculosis (Mtb) highly resistant to antibiotics constitute a public health issue, since tuberculosis still constitutes the primary cause of death in the world due to bacterial infection. Mtb has been shown to produce membrane-derived extracellular vesicles (EVs) containing proteins responsible for modulating the pathological immune response after infection. These natural vesicles were considered a promising alternative to the development of novel vaccines. However, their use was compromised by the observed lack of reproducibility between preparations. In this work, with the aim of developing nanosystems mimicking the extracellular vesicles produced by Mtb, mesoporous silica nanoparticles (MSNs) have been used as nanocarriers of immunomodulatory and vesicle-associated proteins (Ag85B, LprG and LprA). These novel nanosystems have been designed and extensively characterized, demonstrating the effectiveness of the covalent anchorage of the immunomodulatory proteins to the surface of the MSNs. The immunostimulatory capacity of the designed nanosystems has been demonstrated by measuring the levels of pro- (TNF) and anti-inflammatory (IL-10) cytokines in exposed macrophages. These results open a new possibility for the development of more complex nanosystems, including additional vesicle components or even antitubercular drugs, thus allowing for the combination of immunomodulatory and bactericidal effects against Mtb.

The rise of antibiotic resistance and the growing number of biofilm-related infections make bacterial infections a serious threat for global human health. Nanomedicine has entered into this scenario by bringing new alternatives to design and develop effective antimicrobial nanoweapons to fight against bacterial infection. Among them, mesoporous silica nanoparticles (MSNs) exhibit unique characteristics that make them ideal nanocarriers to load, protect and transport antimicrobial cargoes to the target bacteria and/or biofilm, and release them in response to certain stimuli. The combination of infection-targeting and stimuli-responsive drug delivery capabilities aims to increase the specificity and efficacy of antimicrobial treatment and prevent undesirable side effects, becoming a ground-breaking alternative to conventional antibiotic treatments. This review focuses on the scientific advances developed to date in MSNs for infection-targeted stimuli-responsive antimicrobials delivery. The targeting strategies for specific recognition of bacteria are detailed. Moreover, the possibility of incorporating anti-biofilm agents with MSNs aimed at promoting biofilm penetrability is overviewed. Finally, a comprehensive description of the different scientific approaches for the design and development of smart MSNs able to release the antimicrobial payloads at the infection site in response to internal or external stimuli is provided.

Mesoporous bioactive glass nanospheres (NanoMBGs) have high potential for clinical applications. However, the impact of these nanoparticles on the immune system needs to be addressed. In this study, the biocompatibility of SiO2-CaO NanoMBGs was evaluated on different mouse immune cells, including spleen cells subsets, bone marrow-derived dendritic cells (BMDCs), or cell lines like SR.D10 Th2 CD4+ lymphocytes and DC2.4 dendritic cells. Flow cytometry and confocal microscopy show that the nanoparticles were rapidly and efficiently taken up in vitro by T and B lymphocytes or by specialized antigen-presenting cells (APCs) like dendritic cells (DCs). Nanoparticles were not cytotoxic and had no effect on cell viability or proliferation under T-cell (anti-CD3) or B cell (LPS) stimuli. Besides, NanoMBGs did not affect the balance of spleen cell subsets, or the production of intracellular or secreted pro- and anti-inflammatory cytokines (TNF-α, IFN-γ, IL-2, IL-6, IL-10) by activated T, B, and dendritic cells (DC), as determined by flow cytometry and ELISA. T cell activation surface markers (CD25, CD69 and Induced Costimulator, ICOS) were not altered by NanoMBGs. Maturation of BMDCs or DC2.4 cells in vitro was not altered by NanoMBGs, as shown by expression of Major Histocompatibility Complex (MHC) and costimulatory molecules (CD40, CD80, CD86), or IL-6 secretion. The effect of wortmannin and chlorpromazine indicate a role for phosphoinositide 3-kinase (PI3K), actin and clathrin-dependent pathways in NanoMBG internalization. We thus demonstrate that these NanoMBGs are both non-toxic and non-inflammagenic for murine lymphoid cells and myeloid DCs despite their efficient intake by the cells.

Nanoparticles designed for diagnosing and treating different diseases have impacted the scientific research in biomedicine, and are expected to revolutionize the clinic in the near future through a new area called nanomedicine. In the last few years, a new approach in this field has emerged: the use of cell membranes for coating nanoparticles in an attempt to mimic the ability of cells to interface and interact with physiological environments. Although such functions have been replicated through synthetic techniques, many research groups are now employing naturally derived cell membranes to coat different types of nanoparticles in an attempt to improve their performance for a wide range of applications. This review summarizes the literature on nanoparticles coated with cell membranes and, more importantly, aims at inspiring and encouraging new developments to this technology in the biomedical area.

The synthesis of Mobil Composition of Matter 41 (MCM-41) mesoporous silica nanoparticles (MSNs) of controlled sizes and porous structure has been performed at laboratory and pilot plant scales. Firstly, the effects of the main operating conditions (TEOS –Tetraethyl ortosilicate– addition rate, nanoparticle maturation time, temperature, and CTAB –Cetrimonium bromide– concentration) on the synthesis at laboratory scale (1 L round-bottom flask) were studied via a Taguchi experimental design. Subsequently, a profound one-by-one study of operating conditions was permitted to upscale the process without significant particle enlargement and pore deformation. To achieve this, the temperature was set to 60 °C and the CTAB to TEOS molar ratio to 8. The final runs were performed at pilot plant scale (5 L cylindrical reactor with temperature and stirring speed control) to analyze stirring speed, type of impeller, TEOS addition rate, and nanoparticle maturation time effects, confirming results at laboratory scale. Despite slight variations on the morphology of the nanoparticles, this methodology provided MSNs with adequate sizes and porosities for biomedical applications, regardless of the reactor/scale. The process was shown to be robust and reproducible using mild synthesis conditions (2 mL⋅min−1 TEOS addition rate, 400 rpm stirred by a Rushton turbine, 60 min maturation time, 60 °C, 2 g⋅L−1 CTAB, molar ratio TEOS/CTAB = 8), providing ca. 13 g of prismatic short mesoporous 100–200 nm nanorods with non-connected 3 nm parallel mesopores.

Nanoparticles have become a powerful tool in oncology not only as carrier of the highly toxic chemotherapeutic drugs but also as imaging contrast agents that provide valuable information about the state of the disease and its progression. The enhanced permeation and retention effect for loaded nanocarriers in tumors allow substantial improvement of selectivity and safety of anticancer nanomedicines. Additionally, the possibility to design stimuli-responsive nanocarriers able to release their payload in response to specific stimuli provide an excellent control on the administered dosage. The aim of this review is not to present a comprehensive revision of the different theranostic mesoporous silica nanoparticles (MSN) which have been published in the recent years but just to describe a few selected examples to offer a panoramic view to the reader about the suitability and effectiveness of these nanocarriers in the oncology field.

Nanomaterials have unique properties and characteristics derived from their shape and small size that are not present in bulk materials. If size and shape are decisive, the synthesis method used, which determines the above parameters, is equally important. Among the different nanomaterial’s synthesis methods, we can find chemical methods (microemulsion, sol-gel, hydrothermal treatments, etc.), physical methods (evaporation-condensation, laser treatment, etc.) and biosynthesis. Among all of them, the use of laser ablation that allows obtaining non-toxic nanomaterials (absence of foreign compounds) with a controlled 3D size, has emerged in recent years as a simple and versatile alternative for the synthesis of a wide variety of nanomaterials with numerous applications. This manuscript reviews the latest advances in the use of laser ablation for the synthesis of silicon-based nanomaterials, highlighting its usefulness in the prevention of bacterial infection.

Mesoporous silica nanoparticles have attracted much attention in recent years as drug and gene delivery systems for biomedical applications. Among their most beneficial features for biomedicine, we can highlight their biocompatibility and their outstanding textural properties, which provide a great loading capacity for many types of cargos. In the context of cancer nanomedicine, combination therapy and gene transfection/silencing have recently been highlighted as two of its most promising fields. In this review, we aim to provide an overview of the different small molecule drug-nucleic acid co-delivery combinations that have been developed using mesoporous silica nanoparticles as carriers. By carefully selecting the chemotherapeutic drug and nucleic acid cargos to be co-delivered by mesoporous silica nanoparticles, different therapeutic goals can be achieved by overcoming resistance mechanisms, combining different cytotoxic mechanisms, or providing an additional antiangiogenic effect. The examples here presented highlight the great promise of this type of strategies for the development of future therapeutics.

Mesoporous silica nanoparticles have been broadly applied as drug delivery systems owing to their exquisite features, such as excellent textural properties or biocompatibility. However, there are various biological barriers that prevent their proper translation into the clinic, including: (1) lack of selectivity toward tumor tissues, (2) lack of selectivity for tumoral cells and (3) endosomal sequestration of the particles upon internalization. In addition, their open porous structure may lead to premature drug release, consequently affecting healthy tissues and decreasing the efficacy of the treatment. First, this review will provide a comprehensive and systematic overview of the different approximations that have been implemented into mesoporous silica nanoparticles to overcome each of such biological barriers. Afterward, the potential premature and non-specific drug release from these mesoporous nanocarriers will be addressed by introducing the concept of stimuli-responsive gatekeepers, which endow the particles with on-demand and localized drug delivery.

The enormous versatility of mesoporous silica nanoparticles permits the creation of a large number of nanotherapeutic systems for the treatment of cancer and many other pathologies. In addition to the controlled release of small drugs, these materials allow a broad number of molecules of a very different nature and sizes. In this review, we focus on biogenic species with therapeutic abilities (proteins, peptides, nucleic acids, and glycans), as well as how nanotechnology, in particular silica-based materials, can help in establishing new and more efficient routes for their administration. Indeed, since the applicability of those combinations of mesoporous silica with bio(macro)molecules goes beyond cancer treatment, we address a classification based on the type of therapeutic action. Likewise, as illustrative content, we highlight the most typical issues and problems found in the preparation of those hybrid nanotherapeutic materials.

Bone diseases, such as bone cancer, bone infection and osteoporosis, constitute a major issue for modern societies as a consequence of their progressive ageing. Even though these pathologies can be currently treated in the clinic, some of those treatments present drawbacks that may lead to severe complications. For instance, chemotherapy lacks great tumor tissue selectivity, affecting healthy and diseased tissues. In addition, the inappropriate use of antimicrobials is leading to the appearance of drug-resistant bacteria and persistent biofilms, rendering current antibiotics useless. Furthermore, current antiosteoporotic treatments present many side effects as a consequence of their poor bioavailability and the need to use higher doses. In view of the existing evidence, the encapsulation and selective delivery to the diseased tissues of the different therapeutic compounds seem highly convenient. In this sense, silica-based mesoporous nanoparticles offer great loading capacity within their pores, the possibility of modifying the surface to target the particles to the malignant areas and great biocompatibility. This manuscript is intended to be a comprehensive review of the available literature on complex bone diseases treated with silica-based mesoporous nanoparticles—the further development of which and eventual translation into the clinic could bring significant benefits for our future society.

The use of nanomaterials for the treatment of solid tumours is receiving increasing attention by the scientific community. Among them, mesoporous silica nanoparticles (MSNs) exhibit unique features that make them suitable nanocarriers to host, transport and protect drug molecules until the target is reached. It is possible to incorporate different targeting ligands to the outermost surface of MSNs to selectively drive the drugs to the tumour tissues. To prevent the premature release of the cargo entrapped in the mesopores, it is feasible to cap the pore entrances using stimuli-responsive nanogates. Therefore, upon exposure to internal (pH, enzymes, glutathione, etc.) or external (temperature, light, magnetic field, etc.) stimuli, the pore opening takes place and the release of the entrapped cargo occurs. These smart MSNs are capable of selectively reaching and accumulating at the target tissue and releasing the entrapped drug in a specific and controlled fashion, constituting a promising alternative to conventional chemotherapy, which is typically associated with undesired side effects. In this review, we overview the recent advances reported by the scientific community in developing MSNs for antitumor therapy. We highlight the possibility to design multifunctional nanosystems using different therapeutic approaches aimed at increasing the efficacy of the antitumor treatment.

Based on an already tested laboratory procedure, a new magnetron sputtering methodology to simultaneously coat two-sides of large area implants (up to ~15 cm2) with Ti nanocolumns in industrial reactors has been developed. By analyzing the required growth conditions in a laboratory setup, a new geometry and methodology have been proposed and tested in a semi-industrial scale reactor. A bone plate (DePuy Synthes) and a pseudo-rectangular bone plate extracted from a patient were coated following the new methodology, obtaining that their osteoblast proliferation efficiency and antibacterial functionality were equivalent to the coatings grown in the laboratory reactor on small areas. In particular, two kinds of experiments were performed: Analysis of bacterial adhesion and biofilm formation, and osteoblasts−bacteria competitive in vitro growth scenarios. In all these cases, the coatings show an opposite behavior toward osteoblast and bacterial proliferation, demonstrating that the proposed methodology represents a valid approach for industrial production and practical application of nanostructured titanium coatings.

Both the prevalence of antibiotic resistance and the increased biofilm-associated infections are boosting the demand for new advanced and more effective treatment for such infections. In this sense, nanotechnology offers a ground-breaking platform for addressing this challenge. This review shows the current progress in the field of antimicrobial inorganic-based nanomaterials and their activity against bacteria and bacterial biofilm. Herein, nanomaterials preventing the bacteria adhesion and nanomaterials treating the infection once formed are presented through a classification based on their functionality. To fight infection, nanoparticles with inherent antibacterial activity and nanoparticles acting as nanovehicles are described, emphasizing the design of the carrier nanosystems with properties targeting the bacteria and the biofilm.