1 .- Development of Silver-Silica nanocarriers and their stabilisation in solid materials against pathogen bacteria. Towards advanced nano-antibiotics, wound dressing and anti-biofilm surfaces. SiSi4Bacter – PDTC/COL-QUI/1515/2020 FCT MEC
Funding: 233.032,55 Euros
PI: Dr. Javier Fernández-Lodeiro
CoPI: Dr. Carlos Lodeiro
Bacteria induced-infectious are a worldwide problem and responsible for numerous cases of morbidity and mortality.1 For instance, wound infections in diabetic patients, increasingly lead to amputations; as a consequence of bacterial infections that do not respond to the administration of conventional drugs.2 The over-use of antibiotics has resulted in the spread of resistant bacteria. In consequence, there is an urgent need to develop new antimicrobial agents towards pathogenic bacteria. In such a situation, silver-based materials, that that were already widely used by ancient civilizations, has resurfaced as a potent therapeutic option, as evidenced by the increasing number of publications and patents related to the application of silver materials.3,4
Actually, the manipulation of this metal at the nano-metric scale to engineer nanoparticles, has reinforced its therapeutic effectscompared with their silver-bulk conunterpart.5 In recent decades, the fine control in silver colloidal chemistry has allowed the synthesis of AgNPs in wide range of shapes and sizes.6 Note that AgNPs show different susceptibility to oxidation (therefore differentiated anti-microbial effect) depending on their size and shape.7
Additionally to the ionic silver release effect, surface charge,8,9 and/or molecular functionalization (e.g. antibiotics drugs)10 have been shown improve the antimicrobial effects of Ag, or even AuNPs.8 As an example between many others, our group has discovered a synthetic route to produce silver NPs in sizes of 15 or 25 nm using tetracycline as a reducing and stabilizing agent. The as so synthesized NPs showed potent antibacterial effects against Gram+ and Gram- pathogenic bacteria. More importantly, a potent antimicrobial effect against tetracycline-resistant bacteria was also observed.11
Unfortunately, there is still a long way to properly implement this “Holy Grail” biocide. Common drawbacks that silver AgNPs or their organically functionalized analogues present are related to their colloidal stability in biological medium. The aggregation process that, usually, AgNPs undergo/suffer can hinder their antimicrobial effect.12 On the other hand, the high oxidation tendency can hinders their consistent application as a bacterial agent during long time periods.13 Therefore, while the benefits of AgNPs are attracting increasing attention, several publications have pointed out potential adverse effects from the overuse of silver, such as ecosystem disturbance,14 health effects15 or even bacterial resistance to silver.12 At this stage, silver NPs represent a new hope, but conscious use should be considered since early stage to avoid the repetition of past mistakes. To overcome this situation, a coating where Ag NPs are immobilized and containable, can permit the control of ionic silver release in solution, the subsequent organic functionalization and also with a biocompatible character, can become a powerful strategy that will allow the implementation of AgNPs as a safe antibacterial agent in a multitude of applications.
With these considerations in mind, we propose the synthesis of a novel library of nanocarriers based on silver and silica (Ag@Si, Ag@Si@Simes and Ag@GAP@Simes) for the application in bacteriological control. The design proposed here would be flexible and convenient to control the bacterial adhesion properties, as well as load and release behaviour of drug and silver ionic species. The nanocarriers will be conjugated with commercial antimicrobial drugs (Amikacin, Kantamycin Oxacillin and Doxorubicin) in order to study cytotoxicity, bacterial adhesion properties, drug/ionic silver release as well as analysis of the antimicrobial properties against pathogenic Gram+ and Gram- bacteria. Furthermore, stabilization of nanocarriers in PVA hydrogels and surface deposition via electrospray technics are proposed to obtain advanced antimicrobial wound dressing and surfaces.
2 .- Novel synthetic methodologies for metal nanocatalyst based in Gold, Palladium and Platinum and the study of their catalytic performance in key reactions.
PI: Dr. Adrián Fernández-Lodeiro
CoPI: Dr. Javier Fernández-Lodeiro
Fungind: 50,000.00 Euros
Catalysis is one of the essential processes in chemistry. With the increases in global pollutants, contamination leads to a devastating global climate change and urgent needs to findand develop new, fast, and greener chemical processes and methodologies. Renewable energy sources, decontamination of wastewater, and reduction of toxic gases emitted into theatmosphere or faster and cleaner reactions that lead to crucial compounds in the synthetic chemistry field are only a few examples of catalysis plays a critical role. Noble metals,such as platinum, palladium, gold or silver, are widely used in catalyst processes. Their remarkable and sometimes unique performance in catalytic reaction systems are well known;however, one of the main drawbacks is the scarce availability. In this sense, it is the responsibility of scientists to seek solutions for the present problems, anticipate those of thefuture and start promoting alternatives. The use of Noble metals in homogeneous and heterogeneous catalytic applications is of tremendous interest. The interest increased withnovel methodologies in the nanotechnology and catalysis fields. It is possible to finely tune the nanocatalysis up to the atomic level, increasing the population’s surface area andactive centres. It will lead to a drastic reduction of metal needed in comparison with bulk catalysers. Other significant advantages of the nanocatalyst are the possibility to tune themorphology, composition and electronic properties. These advantages can enhance the catalytic activity and stability, critical concepts in the catalysis area. A quick look at theliterature can give the impression that there are already enough methodologies for noble metal nanomaterial synthesis, but the wet chemical approach to produce nanoparticles isfar from complete. The ligands and reducing agents used to control the nanomaterials’ synthesis are surprisingly short, although size, shape and properties are highly dependent onthem. Some synthesis requires several steps reactions, time-consuming procedures or elevated temperatures. Also, the use of organic solvents, strong reducers or toxic compoundsis widely reported. A slight variation in the reaction system can lead to a better process due to modifying the pH, protonation states, redox potential, ionic strength or solubility. Itcan lead to better catalytic properties, faster synthesis, reduced toxicity and allows scalable reactions. Low toxic chemicals, cheap reagents, short reaction times, and moderatetemperatures are preferential and are an essential field of study. Scalable methodologies, environmentally friendly, obtention of highly monodisperse nanoparticles, or a precisecontrol in the functionalisation are some of the challenges that nanoscience is facing nowadays. We propose a simple but elegant approach for advanced synthetic routes of noblemetal nanocatalyst. Based on the well-known oxidation-reduction concepts and our previous expertise in the area, different abundant metals will be applied as reducing agents toprepare more sustainable gold, palladium and platinum nanomaterials. Interestingly, this methodology for the synthesis of metal nanoparticles may not look new. Potters andglassmakers have been using nanomaterial during past centuries to obtain different colours in their creations. A detailed study in their composition during recent years shows thatthey were using multivalent elements such as antimuonium, tin or bismuth to reduce and obtention silver and copper nanomaterials in a silicate substrate, and therefore a variety ofcolours and properties. The design that we propose here would be flexible and convenient to obtain new nanoparticles. The presence of these metals in the reaction medium canimpact the formation and growth of the new nanomaterials, giving birth to new structures and composites that can improve catalytic efficiency. It is worth noticing that any”contamination” of these metals in the final product can positively impact their important catalytic properties. Two well-known methodologies will be applied to achieve this goal,such as direct synthesis and seed-mediated synthesis. Besides, their recovery with bulk or mesoporous silica will be applicated to increase stability and efficiency. To check thecatalytic activity, two well-known reactions will be performed to give us the actual efficiency of these new synthetic routes once compared with the literature. The final goal is to obtain new and more sustainable synthetic routes for nanomaterials with a simple, fast, environmentally friendly, and cheap methodology, contributing with our effort to an essential advance in the nano-chemistry area.
3 . Unlocking the secrets of sumoylation and phosphorylation crosstalk in neurodegeneration using new sumo/phospho-nano traps and quantitative proteomics.
PI: Dr. Hugo M. Santos
Fungind: 50,000.00 Euros
Parkinson, Alzheimer, and brain cancer are characterized by malfunction of cellular signalling networks as a consequence of deregulation of a delicate mechanism of crosstalk between protein phosphorylation and sumoylation. Understanding how phosphorylation and sumoylation impacts cellular signalling networks and its role in disease, has eluded the research community to date because they are dynamic, both occurring at low abundance and both are linked to each other in a complex equilibrium where phosphorylation can either enhance or inhibit sumoylation leading to conformational changes of the substrate protein, altering its activity and function. Herein, a three-dimensional (3D) approach is proposed to overcome these challenges. This 3D method encompasses capturing sumoylated-proteins and phosphorylated peptides at a given time, in a given space and under a given equilibrium using new sumo/phospho-nano traps and quantitative proteomics. We propose to apply this workflow to study the role of sumoylation and phosphorylation crosstalk in brain neurodegeneration and cancer in mice as a consequence exposure to ultrafine particulate matter present in air pollution. The identification of specific alterations of phosphorylation and sumoylation crosstalk and its functional impact will cast light in the mechanisms of neurodegeneration and cancer that can be particularly interesting to select potential targets for new drugs to slow the development and progression of neurodegeneration.