Nanocolumnar coatings on implants exhibiting antibacterial properties

Trabajo presentado en la 2nd International Conference on Nanomaterials Applied to Life Sciences 2020 (NALS 2020), celebrada en Madrid (España), del 29 al 31 de enero de 2020Addressing the problem of infection from the very first stage, i.e. inhibiting the formation of the bacterial biofilm, is a crucial step to prevent implant rejection. Nanocolumnar coatings exhibiting antibacterial properties have been fabricated by oblique deposition with magnetron sputtering [1]. The formation of nanocolumns (Fig.1) is the result of the effects of atomic shadowing when the atoms reach the surface along an inclined direction [2]. This technique is environmentally friendly: it is carried out at RT and does not involve chemical products (no recycling problems). Such methodology have been tested in a semiindustrial scale reactor, successfully coating in a single step the two sides of fixation plates for bone fractures [3]. Several in vitro experiments have been performed: analysis of bacterial adhesion and biofilm formation, analysis of osteoblast proliferation and mitochondrial activity, and osteoblasts–bacteria competitive growth scenarios, the latter also named “Race for the Surface” competition. In all these cases, the coatings show an opposite behavior toward osteoblast and bacterial proliferation [1,3]. Moreover, they are effective against Gram positive (S. aureus) and Gram negative (E. coli) bacteria [4]. Finally, when a synergic route is followed and the coatings are functionalized with Te nanorods, the antibacterial properties are enhanced, since Te adds contact-killing (Fig. 2), i.e. bactericidal effect, whilst the biocompatibility is preserved [4].MINECO and Fundación Domingo Martínez for funding. J.M.G.-M. thanks the Fulbright Commissio

Tellurium-based nanomaterials for advanced biomedical applications

Tesis doctoral presentada para lograr el título de Doctor por la Northeastern University, Chemical Engineering.--06-04-2022Two significant concerns that the healthcare system is facing are cancer and antimicrobial resistance (AMR) to antibiotics. The integumentary (skin) system is particularly affected by these problems since they can occur at the same time, worsening the chances of survival for the patients. Although much effort has been made in the past, there are no definitive solutions yet. Nanotechnology may overcome some limitations of currently available treatments, by reducing cytotoxicity and increasing cell specificity, thus leading to reduced side-effects or higher drug efficacy. While nanotechnology may offer some benefits, traditional synthesis methods of nanomaterials are a threat to both the environment and society by using costly and contaminant chemicals. Therefore, synthesis techniques that do not require toxic reagents are necessary for broader use.In the present thesis, the author aims to tackle both AMR and cancer using a novel approach in nanomedicine: tellurium-based nanomaterials that are fabricated using less hazardous processes. Specifically, the use of starch-based tellurium nanowires was compared with traditional chemical approaches, demonstrating that the less hazardous synthesized materials have enhanced cytotoxic properties towards melanoma cells without damaging healthy tissues. Additionally, the nanowire structure was studied in depth with the objective to re-use it to synthesize nanocomposites incorporating noble nanoparticles such as palladium and platinum ones. The noble metal-chalcogen nanocomposites were characterized, showing different composition and morphology, as well as, antibacterial activity against AMR bacterial strains, in particular, multidrug resistant Escherichia coli and methicillin-resistant Staphylococcus aureus, at concentrations ranging from 10 to 100 μg/mL of both nanocomposites, over a 24h period. Moreover, cell studies were completed with human dermal fibroblasts and melanoma cells for five days, showing no significant cytotoxic effect at nanocomposite concentrations up to 25 μg/mL, while triggering a dose-dependent anticancer effect in the same range. The combined effect of the metal-ion release and the shape of the nanocomposite was identified as the main mechanism of action of the nanostructure

Nano-Tellurium (Te)-Titanioum Synergetic Antibacterial Coatings for Biomedical Applications

Trabajo presentado en el AIChE Annual Meeting (2019), celebrado en Orlando, Florida (Estado Unidos), del 10 al 15 de noviembre de 2019Two different kind of nanocolumnar titanium coatings were prepared using two sputtering systems with very different features -a laboratory setup and semi-industrial equipment-, possessing different morphologies -150 nm long columns tilted 20° from the normal and 300 nm long ones tilted 40°, respectively-. The coatings exhibit similar antibacterial properties against Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli) bacteria. Therefore, a green chemistry route was followed for the synthesis of tellurium nanostructures, that are used as coating agents for the metallic surfaces. As a consequence, the antibacterial properties were enhanced, especially for the long nanocolumns case. The biocompatibility was preserved in all the nanostructured coatings for osteoblasts cells. Besides, different tellurium nanostructures -both nanoparticles and nanowires- were used for the coating of these metallic surfaces, predicting different enhancements in the biocompatibility of the structures. Besides, anticancer studies were performed. Therefore, a new nanotellurium-based functionalization of titanium metallic surfaces is presented with an enhancement of the biomedical applications of these coatings, that can be used in multiple applications

Green Synthesis of a Synergetic Structure of Tellurium Nanowires and Metallic Nanoparticles for Biomedical Applications

Trabajo presentado en el AIChE Annual Meeting (2019), celebrado en Orlando, Florida (Estado Unidos), del 10 al 15 de noviembre de 2019Statement of Purpose: Health care system is facing significant concerns nowadays such as antimicrobial resistance and cancer. New approaches should be considered, and nanotechnology has been found as a powerful solution to them. Current synthetic methodologies for production of nanoparticles, based on physicochemical standards are known to be easy-to-get straightforward. Nevertheless, there is a cost associated with the limitations that should be overcome from these approaches, such as the production of toxic by-products or the lack of biocompatibility of the products. Therefore, new methods are needed, and green chemistry offers itself as a suitable and novel answer, achieving a safe and environmentally-friendly design, manufacture and use of chemical products. In this research, tellurium nanowires were synthesized using a green synthesis methodology (TeNWs). They were characterized in terms of structure and composition and tested for anticancer, antibacterial and cytotoxicity properties. Then, TeNWs were used for the synthesis of metallic nanoparticles in an easy and straightforward method with no need of reducing agent that was completed within 1 minute of reaction. Nanoparticles were characterized, and the synthetic process was compared with the ones described in literature, with the aim to compare the methods in terms of chemical needed, reaction conditions and economic implications. Methods: Tellurium nanowires were prepared using a hydrothermal reaction. The environmentally-friendly approach led to the use of telluric acid and starch as a unique reducing agent. Once purified, tellurium nanowires were used as a template for the growth of metallic nanoparticles (such as platinum and palladium) in a quick method with no need of additional reducing agent at room temperature. The structure containing both metallic nanoparticles and nanowires was known as synergy. Besides, biocompatibility and anticancer tests of both structures – the synergy and the nanowires - with human tissue were accomplished, growing human dermal fibroblast (HDF) cells and melanoma cells in media in the presence of both nanosystems. After an incubation time of 5 days, the cell growth was analyzed using MTS assay. Furthermore, antibacterial properties were tested against Escherichia Coli and Staphyloccocus Aureus. Results: It was demonstrated that green synthesized tellurium nanowires can be used as a template for the growth of metallic nanoparticles in a quick reaction that takes places in 1 minute, at room temperature with no need of stirring and reducing agent. TEM images of both tellurium nanowires and metallic nanoparticles were taken (Fig.1), showing nanoparticles with a constant distribution size attached to the tellurium nanowires, which were quickly released from the structure. The chemistry of the samples was confirmed using EDX analysis, showing the distinct peaks of tellurium and the ones corresponding to each one of the metals. In vitro cytotoxicity assays were performed with human dermal fibroblasts (HDF) cells. The experiments showed that the use of green nanostructures, enhanced the growth of the cells in comparison with the control. Furthermore, anticancer and antimicrobial studies showed an improved performance of the synergetic structure compared to the bare nanowires structures, causing a higher depletion of cell viability. Conclusions: Current and main methods to synthesize nanostructures, both nanowires and nanoparticles, use approaches which employ chemical methods. The weakness of these procedures (extreme reaction conditions, production of toxic byproducts…) calls for a necessity of alternative approaches. Green chemistry can be used to overcome these drawbacks. Here, green-synthesized tellurium nanowires were compared with chemically-synthesized structures to show that the first ones have an enhanced biocompatibility and anticancer properties over the ones synthesized using traditional methods. Besides, it was demonstrated that tellurium nanowires synthesized using starch can be used for the controllable and quick growth of metallic nanoparticles

Aloe Vera-Mediated Green Synthesis of Tellurium Nanostructures with Both Antimicrobial and Anticancer Activity

Trabajo presentado en el AIChE Annual Meeting (2019), celebrado en Orlando, Florida (Estado Unidos), del 10 al 15 de noviembre de 2019Antimicrobial resistance to antibiotics is a huge concern that presents significant challenges to modern healthcare. Thus, an alternative solution that does not require the use of antibiotics is needed. One of the most promising methodologies comes from the implementation of nanotechnology. Unlike antibiotics, bacteria are unable to develop resistance to nanoparticles. Many methods for synthesis of various types of nanostructures have been reported. Nevertheless, they are often accompanied by significant drawbacks such as cost, harsh processing conditions, and production of toxic by-products that are a concern for both the environment and society. In this work, an environmentally-friendly and cost-effective approach for synthesis of tellurium nanorods in aqueous media have been developed using aloe vera extract as a unique reducing agent. Nanorods were characterized using Transmission Electron Microscopy and Energy-Dispersive X-Ray Spectroscopy to determine size, morphology and composition. Resulting nanoparticles with a length 100±19 nm and width of 5±2 were produced. Nanoparticles were also characterized and tested for their ability to inhibit bacterial growth. A decay in bacterial growth after 24 hours was achieved for both Staphylococcus aureus and Escherichia coli at tellurium nanoparticle concentrations from 5 to 75 µg/mL. Biocompatibility assays were also performed, and the nanoparticles showed no cytotoxic effects for human dermal fibroblast cells after 48 hours. Anticancer properties were tested as well, and results indicated that the nanoparticles (in concentrations ranging from 5 to 75 µg/mL) were able to delay cancer cell proliferation. Aloe vera extracts afforded synthesis of tellurium nanoparticles in a quick, cost-effective and completely green approach that showed both antimicrobial and anticancer effects with low cytotoxicity for healthy cells

In Situ Generation of Metal-Oxide Nanoparticles on Top of a Green- Synthesized Tellurium Nanowire Template and the Biomedical Study of the Synergetic Structure

Trabajo presentado en el AIChE Annual Meeting, celebrado de forma virtual del 16 al 20 de noviembre de 2020Two of the major concerns that the healthcare system is facing nowadays are cancer and antimicrobial resistance (AMR) to antibiotics. Nanotechnology appears as a suitable solution, which might overcome some limitations of current available treatments. Despite of the advances in the nanoscale, there is a need to find alternatives to the traditional synthesis of nanomaterials, which suppose a threat to both the environment and society. In this context, Green Nanotechnology is presented as an answer, with cost-effective and environmentally-friendly approaches for nanoparticles synthesis. In the present work, starch-mediated Tellurium nanowires were employed as a template for the in-situ growth of palladium and platinum nanostructures. The noble metal-chalcogenide nanocomposites were characterized for their biomedical applications, with both green-mediated synergetic composites showing antibacterial activity against AMR bacterial strains, both Gram negative (MDR Escherichia coli) and positive (Methicillin resistant Staphylococcus aureus) bacteria, at concentrations from 10 to 100 µg/mL over a 24-hour time period. Moreover, cell studies were done with human dermal fibroblast (HDF) and melanoma cells for 5 days, showing no significant cytotoxic effect at concentrations up to 25 µg/mL, while triggering a dose-dependent anticancer effect in the same rage of concentrations. Therefore, the use of noble metalchalcogenide nanocomposites is proposed as a novel green nanotechnologicalbased platform for biomedical applications

Nanocarrier drug resistant tumor interactions: novel approaches to fight drug resistance in cancer

Cancer is one of the biggest healthcare concerns in our century, a disease whose treatment has become even more difficult following reports of drug-resistant tumors. When this happens, chemotherapy treatments fail or decrease in efficiency, leading to catastrophic consequences to the patient. This discovery, along with the fact that drug resistance limits the efficacy of current treatments, has led to a new wave of discovery for new methods of treatment. The use of nanomedicine has been widely studied in current years as a way to effectively fight drug resistance in cancer. Research in the area of cancer nanotechnology over the past decades has led to tremendous advancement in the synthesis of tailored nanoparticles with targeting ligands that can successfully attach to chemotherapy-resistant cancer by preferentially accumulating within the tumor region through means of active and passive targeting. Consequently, these approaches can reduce the off-target accumulation of their payload and lead to reduced cytotoxicity and better targeting. This review explores some categories of nanocarriers that have been used in the treatment of drug-resistant cancers, including polymeric, viral, lipid-based, metal-based, carbon-based, and magnetic nanocarriers, opening the door for an exciting field of discovery that holds tremendous promise in the treatment of these tumors

Starch-mediated synthesis of mono- and bimetallic silver/gold nanoparticles as antimicrobial and anticancer agents

Background and aim: Bimetallic silver/gold nanosystems are expected to significantly improve therapeutic efficacy compared to their monometallic counterparts by maintaining the general biocompatibility of gold nanoparticles (AuNPs) while, at the same time, decreasing the relatively high toxicity of silver nanoparticles (AgNPs) toward healthy human cells. Thus, the aim of this research was to establish a highly reproducible one-pot green synthesis of colloidal AuNPs and bimetallic Ag/Au alloy nanoparticles (NPs; Ag/AuNPs) using starch as reducing and capping agent. Methods: The optical properties, high reproducibility, stability and particle size distribution of the colloidal NPs were analyzed by ultraviolet (UV)–visible spectroscopy, dynamic light scattering (DLS) and ζ-potential. The presence of starch as capping agent was determined by Fourier transform infrared (FT-IR) spectroscopy. The structural properties were studied by X-ray diffraction (XRD). Transmission electron microscopy (TEM) imaging was done to determine the morphology and size of the nanostructures. The chemical composition of the nanomaterials was determined by energy-dispersive X-ray spectroscopy (EDS) and inductively coupled plasma mass spectrometry (ICP-MS) analysis. To further study the biomedical applications of the synthesized nanostructures, antibacterial studies against multidrug-resistant (MDR) Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) were conducted. In addition, the NPs were added to the growth media of human dermal fibroblast (HDF) and human melanoma cells to show their cytocompatibility and cytotoxicity, respectively, over a 3-day experiment. Results: UV–visible spectroscopy confirmed the highly reproducible green synthesis of colloidal AuNPs and Ag/AuNPs. The NPs showed a face-centered cubic crystal structure and an icosahedral shape with mean particle sizes of 28.5 and 9.7 nm for AuNPs and Ag/AuNPs, respectively. The antibacterial studies of the NPs against antibiotic-resistant bacterial strains presented a dose-dependent antimicrobial behavior. Furthermore, the NPs showed cytocompatibility towards HDF, but a dose-dependent anticancer effect was found when human melanoma cells were grown in presence of different NP concentrations for 72 hours. Conclusion: In this study, mono- and bimetallic NPs were synthesized for the first time using a highly reproducible, environmentally friendly, cost-effective and quick method and were successfully characterized and tested for several anti-infection and anticancer biomedical applications

Comparison of cytocompatibility and anticancer properties of traditional and green chemistry-synthesized tellurium nanowires

[Background] Tradiditional physicochemical approaches for the synthesis of compounds, drugs, and nanostructures developed as potential solutions for antimicrobial resistance or against cancer treatment are, for the most part, facile and straightforward. Nevertheless, these approaches have several limitations, such as the use of toxic chemicals and production of toxic by-products with limited biocompatibility. Therefore, new methods are needed to address these limitations, and green chemistry offers a suitable and novel answer, with the safe and environmentally friendly design, manufacturing, and use of minimally toxic chemicals. Green chemistry approaches are especially useful for the generation of metallic nanoparticles or nanometric structures that can effectively and efficiently address health care concerns.[Objective] Here, tellurium (Te) nanowires were synthesized using a novel green chemistry approach, and their structures and cytocompatibility were evaluated.[Method] An easy and straightforward hydrothermal method was employed, and the Te nanowires were characterized using transmission electron microscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy, and optical microscopy for morphology, size, and chemistry. Cytotoxicity tests were performed with human dermal fibroblasts and human melanoma cells (to assess anticancer properties). The results showed that a treatment with Te nanowires at concentrations between 5 and 100 µg/mL improved the proliferation of healthy cells and decreased cancerous cell growth over a 5-day period. Most importantly, the green chemistry -synthesized Te nanowires outperformed those produced by traditional synthetic chemical methods.[Conclusion] This study suggests that green chemistry approaches for producing Te nanostructures may not only reduce adverse environmental effects resulting from traditional synthetic chemistry methods, but also be more effective in numerous health care applications.Dr María Ujué González reports grants from MINECO, MINECO + EU, and the Government of Autonomous Region of Madrid, CM, during the conduct of the study. Dr Yves Huttel reports grants from MINECO during the conduct of the study. Dr José Miguel García-Martín reports grants from MINECO, MECD, and Fulbright Commission, during the conduct of the study.Peer reviewe