Immunotherapeutic nanoparticles: From autoimmune disease control to the development of vaccines.

The development of nanoparticles (NPs) with potential therapeutic uses represents an area of vast interest in the scientific community during the last years. Recently, the pandemic caused by COVID-19 motivated a race for vaccines creation to overcome the crisis generated. This is a good demonstration that nanotechnology will most likely be the basis of future immunotherapy. Moreover, the number of publications based on nanosystems has significantly increased in recent years and it is expected that most of these developments can go on to experimentation in clinical stages soon. The therapeutic use of NPs to combat different diseases such as cancer, allergies or autoimmune diseases will depend on their characteristics, their targets, and the transported molecules. This review presents an in-depth analysis of recent advances that have been developed in order to obtain novel nanoparticulate based tools for the treatment of allergies, autoimmune diseases and for their use in vaccines. Moreover, it is highlighted that by providing targeted delivery an increase in the potential of vaccines to induce an immune response is expected in the future. Definitively, the here gathered analysis is a good demonstration that nanotechnology will be the basis of future immunotherapy.

Surface chemistry modification of silica nanoparticles alters the activation of monocytes.

Aim: Nanoparticles (NPs) interaction with immune system is a growing topic of study. Materials & methods: Bare and amine grafted silica NPs effects on monocytes/macrophages cells were analyzed by flow cytometry, MTT test and LIVE/DEAD® viability/cytotoxicity assay. Results: Bare silica NPs inhibited proliferation and induced monocyte/macrophages activation (increasing CD40/CD80 expression besides pro-inflammatory cytokines and nitrite secretion). Furthermore, silica NPs increased cell membrane damage and reduced the number of living cells. In contrast, amine grafted silica NPs did not alter these parameters. Conclusion: Cell activation properties of bare silica NPs could be hindered after grafting with amine moieties. This strategy is useful to tune the immune system stimulation by NPs or to design NPs suitable to transport therapeutic molecules.

Nanoparticles and Immune Cells.

Nanoparticles have gained ground in several fields. However, it is important to consider their potentially hazardous effects on humans, flora, and fauna. Human exposure to nanomaterials can occur unintentionally in daily life or in industrial settings, and the continuous exposure of the biological components (cells, receptors, proteins, etc.) of the immune system to these particles can trigger an unwanted immune response (activation or suppression). Here, we present different studies that have been carried out to evaluate the response of immune cells in the presence of nanoparticles and their possible applications in the biomedical field.

Silicified collagen materials: Modulation of the in vitro and in vivo response.

Collagen derived materials offer distinct advantages over synthetic polymers, considering their natural inherited biocompatibility and mechanical properties. However, because of the extraction procedure, the latter frequently need to be enhanced through the use of different crosslinking methods. Aldehydes are often used for the stabilization of biomaterials but the introduction of crosslinkers slightly alters the protein's surface reactivity hence calling for new biocompatibility studies. At the same time, silicate modification of natural polymers has gained interest within the biomaterials field for their strengthening potential and ease of manipulation, giving rise to different surfaces and bulk materials. In the present work, collagen gels modified with glutaraldehyde (ColGA) or glutaraldehyde and an aminosilane (ColGASi) were evaluated in vitro and in vivo with the aim to obtain biomaterials for wound dressings. The results obtained were compared to those derived from unmodified collagen matrices (Col). In vitro assays focused on the interaction of the materials with elements present in the human blood whereas in vivo assays evaluated their ability to support cell proliferation and angiogenesis for a period of 30 days in a rodent model. Col gels induced an increase in platelet aggregation while ColGA gels decreased it. On the other hand, ColGASi had no effect on platelet aggregation but induced IL-1ß and nitric oxide platelet secretion. All gels induced lower IL-6 levels in PMN cells cultures when compared to controls. Col and ColGA gels decreased IL-1ß concentration whereas ColGASi induced high expression of TGF-ß in PMN cells. All gels decreased nitric oxide secretion but Col and ColGA gels increased IL-1ß production by monocytes. Definitely, all gels induced an anti and pro-inflammatory profile depending on the cell type with which they interact. In vivo, an increased cellular infiltration was observed along with new blood vessel formation in those matrices containing silicified collagen, while glutaraldehyde fixed collagen induced a foreign body reaction and appeared surrounded by a fibrous capsule after 30 days of subcutaneous implantation. Overall, the results obtained show that the silicification of collagen has advantages not only through the enhancement of its mechanical properties but also through the stimulation of the integration of the material with the surrounding tissue.

Dodecenylsuccinic anhydride modified collagen hydrogels loaded with simvastatin as skin wound dressings.

Skin wound healing presents a unique challenge because of its complex healing process. Herein, we developed a hydrophobic wound dressing to incorporate simvastatin, which has potential application in the treatment of ulcers and prevention of wound infection. For that matter, collagen hydrogels were grafted with dodecenylsuccinic anhydride (DDSA). The chemical modification was confirmed by FTIR and solid state 13 C-NMR spectroscopies while the ultrastructure was observed by scanning electron microscope (SEM) images. In contact angle measurements, a higher water droplet angle in DDSA-collagen gels was observed. This was consistent with the swelling assay, in which water absorption was 5.2 g/g for collagen and 1.9 g/g for DDSA-collagen. Additionally, viability and adhesion studies were performed. Cell adhesion decreased ~11% in DDSA-collagen and the number of viable cells showed a tendency to decrease as DDSA concentration increased but it was only significantly lower above concentrations of 12%. Modified gels were loaded with simvastatin showing higher adsorption capacity and lower release. Lastly, the antimicrobial and anti-inflammatory activity of DDSA-collagen materials were assessed. DDSA-collagen hydrogels, either unloaded or loaded with simvastatin showed sustained antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus for 72 hr probably due to the hydrophobic interaction of DDSA chains with bacterial cell walls. The antimicrobial activity was stronger against S. aureus. Collagen hydrogels also presented a prolonged antibacterial activity when they were loaded with simvastatin, confirming the antimicrobial properties of statins. Finally, it was observed that these materials can stimulate resident macrophages and promote an M2 profile which is desirable in wound healing processes.

Evidence of size-dependent effect of silica micro- and nano-particles on basal and specialized monocyte functions.

AIM: To analyze the effect of silica particles on monocyte/macrophage functions. MATERIALS & METHODS: Silica micro- and nanoparticles were obtained by the Stöber method. Their effect on monocyte/macrophage proliferation, activation, membrane integrity and metabolic activity were determined. RESULTS: Silica particles inhibit cell proliferation while 10 nm nanoparticles (NPs) did not affect it. Similarly, silica particles induced strong cell activation. However, 10 nm NPs do not alter IL-12 or nitrite levels. Furthermore, bigger NPs and microparticles increase cell membrane damage and reduce the number of living cells but smallest NPs (10 and 240 nm) did not. CONCLUSION: Cell activation properties of silica particles could be useful tools for immune stimulation therapy, while 10 nm NPs would be suitable for molecule transportation.

Canarypox virus expressing infectious bursal disease VP2 protein as immunogen for chickens.

Canarypox viruses (CNPV) carrying the coding sequence of VP2 protein from infectious bursal disease virus (IBDV) were obtained. These viruses were able to express VP2 protein in vitro and to induce IBDV-neutralizing antibodies when inoculated in specific pathogen-free chickens demonstrating that CNPV platform is usefulness to develop immunogens for chickens.

Canarypox virus expressing infectious bursal disease VP2 protein as immunogen for chickens

Canarypox viruses (CNPV) carrying the coding sequence of VP2 protein from infectious bursal disease virus (IBDV) were obtained. These viruses were able to express VP2 protein in vitro and to induce IBDV-neutralizing antibodies when inoculated in specific pathogen-free chickens demonstrating that CNPV platform is usefulness to develop immunogens for chickens.