"Attacking-Attacking" Anti-biofouling Strategy Enabled by Cellulose Nanocrystals-Silver Materials.

The development of high-performance anti-biofouling surfaces is paramount for controlling bacterial attachment and biofilm growth in biomedical devices, food packing, and filtration membranes. Cellulose nanocrystals (CNCs), a carbon-nanotube-like nanomaterial, have emerged as renewable and sustainable antimicrobial agents. However, CNCs inactivate bacteria under contact-mediated mechanisms, limiting its antimicrobial property mostly to the attached bacteria. This study describes the combination of CNCs with silver nanoparticles (CNC/Ag) as a strategy to increase their toxicity and anti-biofouling performance. CNC/Ag-coated surfaces inactivated over 99% of the attached Escherichia coli and Bacillus subtilis cells compared to 66.9 and 32.9% reduction shown by the pristine CNC, respectively. CNC/Ag was also very toxic to planktonic cells, displaying minimal inhibitory of 25 and 100 µg/mL against B. subtilis and E. coli, respectively. CNC/Ag seems to inactivate bacteria through an "attacking-attacking" mechanism where CNCs and silver nanoparticles play different roles. CNCs can kill bacteria by piercing the cell membrane. This physical membrane stress-mediated mechanism is demonstrated as lipid vesicles release their encapsulated dye upon contact with CNCs. Once the cell membrane is punctured, silver ions can enter the cell passively and compromise the integrity of DNA and other organelles. Inside the cells, Ag+ may damage the cell membrane by selectively interacting with sulfur and nitrogen groups of enzymes and proteins or by harming DNA via accumulation of reactive oxygen species. Therefore, CNC/Ag toxicity seems to combine the puncturing effect of the needle-like CNC and the silver's ability to impair the cell membrane and DNA functionalities.

Catalytic antimicrobial robots for biofilm eradication.

Magnetically driven robots can perform complex functions in biological settings with minimal destruction. However, robots designed to damage deleterious biostructures could also have important impact. In particular, there is an urgent need for new strategies to eradicate bacterial biofilms as we approach a post-antibiotic era. Biofilms are intractable and firmly attached structures ubiquitously associated with drug-resistant infections and destruction of surfaces. Existing treatments are inadequate to both kill and remove bacteria leading to reinfection. Here we design catalytic antimicrobial robots (CARs) that precisely and controllably kill, degrade and remove biofilms with remarkable efficiency. CARs exploit iron oxide nanoparticles (NPs) with dual catalytic-magnetic functionality that (i) generate bactericidal free radicals, (ii) breakdown the biofilm exopolysaccharide (EPS) matrix, and (iii) remove the fragmented biofilm debris via magnetic field driven robotic assemblies. We develop two distinct CAR platforms. The first platform, the biohybrid CAR, is formed from NPs and biofilm degradation products. After catalytic bacterial killing and EPS disruption, magnetic field gradients assemble NPs and the biodegraded products into a plow-like superstructure. When driven with an external magnetic field, the biohybrid CAR completely removes biomass in a controlled manner, preventing biofilm regrowth. Biohybrid CARs can be swept over broad swathes of surface or can be moved over well-defined paths for localized removal with microscale precision. The second platform, the 3D molded CAR, is a polymeric soft robot with embedded catalytic-magnetic NPs, formed in a customized 3D printed mold to perform specific tasks in enclosed domains. Vane-shaped CARs remove biofilms from curved walls of cylindrical tubes, and helicoid-shaped CARs drill through biofilm clogs, while simultaneously killing bacteria. In addition, we demonstrate applications of CARs to target highly confined anatomical surfaces in the interior of human teeth. These 'kill-degrade-and-remove' CARs systems could have significant impact in fighting persistent biofilm-infections and in mitigating biofouling of medical devices and diverse surfaces.

On the formation of protein corona on colloidal nanoparticles stabilized by depletant polymers.

To counter the undesired colloidal destabilization of nanoparticles in biologically-compatible media of high ionic strength (i.e. NaCl, phosphate buffer), polymers can be added to nanoparticle suspensions that will be used in biomedical applications. In these suspensions, polymers can promote high colloidal stability by manifestation of steric and/or depletion forces. However, little is known about the influence of these polymers on the interactions between nanoparticles and the biological components of the organism, such as proteins and cells. In this work, it was shown that the addition of the polymers (i) Pluronic-F127 (PF127), (ii) polyethylene glycol (PEG) of different molecular weights - 1.5, 12 and 35 kDa - and (iii) the protein bovine serum albumin (BSA) on colloidal silica nanoparticles (CSNPs; 135 nm) dispersed in phosphate-buffered saline (PBS) largely alter their colloidal stability through different mechanisms. Although all polymers were adsorbed on the CSNP surface, BSA maintained the CSNP dispersion in the medium by electrosteric stabilization mechanisms, while PEG and PF127 led to the occurrence of depletion forces between the particles. In addition, it was found that the interactions between polymers and CSNPs did not prevent proteins to access the nanoparticles' surface and have minimal effect on the formation of the protein corona when they were incubated in human blood plasma. On the other hand, BSA had a greater effect on the CSNP protein corona profile compared to other polymers (PEG and PF127). Together, these results confirm that biocompatible polymers PEG and PF127 can be used as colloidal stabilizing agents for nanoparticles since they preserve the accessibility of biomolecules to the nanoparticle surface, and they have little effect on the protein corona composition.

Silver nanoparticles in dentistry.

OBJECTIVE: Silver nanoparticles (AgNPs) have been extensively studied for their antimicrobial properties, which provide an extensive applicability in dentistry. Because of this increasing interest in AgNPs, the objective of this paper was to review their use in nanocomposites; implant coatings; pre-formulation with antimicrobial activity against cariogenic pathogens, periodontal biofilm, fungal pathogens and endodontic bacteria; and other applications such as treatment of oral cancer and local anesthesia. Recent achievements in the study of the mechanism of action and the most important toxicological aspects are also presented. METHODS: Systematic searches were carried out in Web of Science (ISI), Google, PubMed, SciFinder and EspaceNet databases with the keywords "silver nano* or AgNP*" and "dentist* or dental* or odontol*". RESULTS: A total of 155 peer-reviewed articles were reviewed. Most of them were published in the period of 2012-2017, demonstrating that this topic currently represents an important trend in dentistry research. In vitro studies reveal the excellent antimicrobial activity of AgNPs when associated with dental materials such as nanocomposites, acrylic resins, resin co-monomers, adhesives, intracanal medication, and implant coatings. Moreover, AgNPs were demonstrated to be interesting tools in the treatment of oral cancers due to their antitumor properties. SIGNIFICANCE: The literature indicates that AgNPs are a promising system with important features such as antimicrobial, anti-inflammatory and antitumor activity, and a potential carrier in sustained drug delivery. However, there are some aspects of the mechanisms of action of AgNPs, and some important toxicological aspects arising from the use of this system that must be completely elucidated.

Advances in Dental Materials through Nanotechnology: Facts, Perspectives and Toxicological Aspects.

Nanotechnology is currently driving the dental materials industry to substantial growth, thus reflecting on improvements in materials available for oral prevention and treatment. The present review discusses new developments in nanotechnology applied to dentistry, focusing on the use of nanomaterials for improving the quality of oral care, the perspectives of research in this arena, and discussions on safety concerns regarding the use of dental nanomaterials. Details are provided on the cutting-edge properties (morphological, antibacterial, mechanical, fluorescence, antitumoral, and remineralization and regeneration potential) of polymeric, metallic and inorganic nano-based materials, as well as their use as nanocluster fillers, in nanocomposites, mouthwashes, medicines, and biomimetic dental materials. Nanotoxicological aspects, clinical applications, and perspectives for these nanomaterials are also discussed.