Cracking the immune fingerprint of metal-organic frameworks.

The human body is in a never-ending chess game against pathogens. When the immune system, our natural defence tool, is weakened, these organisms are able to escape, overcoming the body's contingency plan, which results in the body going into a pathological state. To overcome this checkmate status, emerging nanomedicines have been successfully employed as one of the best tactics for boosting the immune response, manipulating the body's defence tools for the specific recognition/elimination of pathological cells via the active ingredient delivery. However, the vast majority of these drug-delivery systems (DDS) are considered to be exclusively passive vehicles, with nanoscale metal-organic frameworks (nanoMOFs) attracting a great deal of attention due to their versatility and ability to carry and deliver exceptional drug payloads and to modulate their biological bypass. Nonetheless, their intrinsic immunogenicity character has been never addressed. Considering the immense possibilities that nanoMOFs offer as a treatment platform, the present study aimed to unveil the immunological fingerprint of MOFs, including an in-deep evaluation of the cellular oxidation balance, the inflammation and recruitment of immune cells and the precise Th1/Th2 cytokine profile that is triggered. This study aims to gain insights that will make more feasible the design of customized immune-active MOF nanoplatforms according to targeted diseases, as the next ace up immune system sleeve.

Eco-friendly extraction of Mastocarpus stellatus carrageenan for the synthesis of gold nanoparticles with improved biological activity.

Carrageenan was extracted from Mastocarpus stellatus using hot water extraction under atmospheric and pressurized conditions. The influence of heating temperature during a non-isothermal heating profile up to temperatures in the range 70-190 °C was studied to evaluate the extraction yields and properties of the carrageenan fraction. Under the selected conditions (130 °C), extracted carrageenan (CMs) was used for the green synthesis of gold nanoparticles (AuNPs). After the optimization of the reaction conditions, the synthesized gold nanoparticles (Au@CMs) were characterized by UV-Vis spectroscopy, Z potential measurements, electron microscopy, and X-ray diffraction analysis, which confirmed the formation of spherical, polycrystalline, and negatively charged nanoparticles with a mean diameter of 14.3 ± 2.1 nm. The study conducted by scanning transmission electron microscopy, energy dispersive X-ray analysis and mapping confirmed the presence of carrageenan stabilizing AuNPs. Finally, Fourier transformed infrared spectroscopy was performed to analyze the functional groups of CMs involved in the reduction and stabilization of AuNPs. The selective cytotoxicity and the antioxidant activity of the Au@CMs were evaluated in different cell lines and compared to the CMs. Au@CMs showed an improved antioxidant capacity in cells under oxidative stress and the induction of apoptosis in a monocytic cell line, while no antitumor effect was observed in a lung endothelial cell line.

Saccorhiza polyschides used to synthesize gold and silver nanoparticles with enhanced antiproliferative and immunostimulant activity.

Over the last years, there has been an increasing trend towards the use of environmentally friendly processes to synthesize nanomaterials. In the case of nanomedicine, the use of bionanofactories with associated biological properties, such as seaweed, has emerged as a promising field of work due to the possibility they open for both the preservation of those properties in the nanomaterials synthesized and/or the reduction of their toxicity. In the present study, gold (Au@SP) and silver (Ag@SP) nanoparticles were synthesized using an aqueous extract of Saccorhiza polyschides (SP). Several techniques showed that the nanoparticles formed were spherical and stable, with mean diameters of 14 ± 2 nm for Au@SP and 15 ± 3 nm for Ag@SP. The composition of the biomolecules in the extract and the nanoparticles were also analyzed. The analyses performed indicate that the extract acts as a protective medium, with the particles embedded in it preventing aggregation and coalescence. Au@SP and Ag@SP showed superior immunostimulant and antiproliferative activity on immune and tumor cells, respectively, to that of the SP extract. Moreover, the nanoparticles were able to modulate the release of reactive oxygen species depending on the concentration. Hence, both nanoparticles have a significant therapeutic potential for the treatment of cancer or in immunostimulant therapy.

Immunostimulant and biocompatible gold and silver nanoparticles synthesized using the Ulva intestinalis L. aqueous extract.

This is the first study to report on the biocompatible and immunogenic properties of one-pot synthesised gold and silver nanoparticles (Au@UI and Ag@UI) using the macroalgae Ulva intestinalis (UI). The UI aqueous extract, Au@UI, and Ag@UI were obtained under sterile conditions and fully characterized by UV-vis spectroscopy, TEM, HRTEM, STEM and FTIR spectroscopy. Moreover, for the first time, the composition of carbohydrates in the UI extract has been reported along with the changes observed after nanoparticle synthesis by size exclusion chromatography, in order to investigate their possible role in the biosynthetic process. This study suggested that the polysaccharide fraction of the extract is involved in the formation and stabilization of the nanoparticles. The potential toxicity of the samples was evaluated using different cell lines and the hemocompatibility was tested in mouse erythrocytes. In addition, ROS production, complement activation and cytokine release were evaluated to determine the immunogenicity. The results showed that Au@UI and Ag@UI exhibit good biocompatibility and hemocompatibility, with the exception of Ag@UI nanoparticles at high concentration, which were hemolytic. The samples induced ROS release and complement activation, two key mechanisms in innate immunity. The samples also induced the release of cytokines from Th1 and Th2 profiles, and other cytokines implicated in the activation of the immune system. Au@UI and Ag@UI were biocompatible and preserved the immunostimulant properties of the UI extract. Hence, Au@UI and Ag@UI could be useful as adjuvants in vaccine development and promote a balanced Th1 and Th2 immune response mediated by ROS production, cytokine release and complement activation.

Chitosan-coated mesoporous MIL-100(Fe) nanoparticles as improved bio-compatible oral nanocarriers.

Nanometric biocompatible Metal-Organic Frameworks (nanoMOFs) are promising candidates for drug delivery. Up to now, most studies have targeted the intravenous route, related to pain and severe complications; whereas nanoMOFs for oral administration, a commonly used non-invasive and simpler route, remains however unexplored. We propose here the biofriendly preparation of a suitable oral nanocarrier based on the benchmarked biocompatible mesoporous iron(III) trimesate nanoparticles coated with the bioadhesive polysaccharide chitosan (CS). This method does not hamper the textural/structural properties and the sorption/release abilities of the nanoMOFs upon surface engineering. The interaction between the CS and the nanoparticles has been characterized through a combination of high resolution soft X-ray absorption and computing simulation, while the positive impact of the coating on the colloidal and chemical stability under oral simulated conditions is here demonstrated. Finally, the intestinal barrier bypass capability and biocompatibility of CS-coated nanoMOF have been assessed in vitro, leading to an increased intestinal permeability with respect to the non-coated material, maintaining an optimal biocompatibility. In conclusion, the preservation of the interesting physicochemical features of the CS-coated nanoMOF and their adapted colloidal stability and progressive biodegradation, together with their improved intestinal barrier bypass, make these nanoparticles a promising oral nanocarrier.

Characterization of the autoimmune response against the nerve tissue S100ß in patients with type 1 diabetes.

Type 1 diabetes results from destruction of insulin-producing beta cells in pancreatic islets and is characterized by islet cell autoimmunity. Autoreactivity against non-beta cell-specific antigens has also been reported, including targeting of the calcium-binding protein S100ß. In preclinical models, reactivity of this type is a key component of the early development of insulitis. To examine the nature of this response in type 1 diabetes, we identified naturally processed and presented peptide epitopes derived from S100ß, determined their affinity for the human leucocyte antigen (HLA)-DRB1*04:01 molecule and studied T cell responses in patients, together with healthy donors. We found that S100ß reactivity, characterized by interferon (IFN)-γ secretion, is a characteristic of type 1 diabetes of varying duration. Our results confirm S100ß as a target of the cellular autoimmune response in type 1 diabetes with the identification of new peptide epitopes targeted during the development of the disease, and support the preclinical findings that autoreactivity against non-beta cell-specific autoantigens may have a role in type 1 diabetes pathogenesis.