Published Work

Green nanotechnology-based zinc oxide (ZnO) nanomaterials for biomedical applications: a review

March 2020

Journal of Physics: Materials

David Medina Cruz

Ebrahim Mostafavi

Ada Vernet Crua

Hamed Barabadi

Veer Shah

Jorge Luis Cholula-Díaz

Gregory Guisbiers

Thomas J Webster

The rise of nanotechnology has brought to the world a new potential and broader perspective of what humanity can achieve through the manipulation of nanoscale. As a consequence, the use of different nanomaterials has revolutionized the industrial and biomedical worlds. Metallic and metal-oxide nanostructures have shown great potential, due to their high surface to volume ratio and high reactivity; and among them, zinc oxide (ZnO) has revealed wider applicability, including nanomedicine, where ZnO nanomaterials have shown great potential, leading to effective interactions with biological membranes and exhibiting antibacterial and anticancer behaviors. However, consistent with several other nanostructures, the synthesis of ZnO nanomaterials is not devoid of drawbacks, such as the production of harmful and toxic byproducts, the use of toxic reagents, the employment of expensive instruments, and the lack of biocompatibility, all of which need to be overcome for extensive functionalization. As a solution, green nanotechnology has allowed the production of ZnO nanostructures using environmentally friendly and cost-effective methods, which are based on the use of living organisms, natural biomolecules and waste materials. Once produced, green-synthesized ZnO nanoparticles have shown enhancements in terms of their cytocompatibility and biomedical properties compared to their traditionally produced counterparts, becoming excellent antibacterial or anticancer agents. These ZnO nanoparticles have also proven valuable materials in combination with wound healing processes and biosensing elements in order to trace small amounts of biomarkers associated with different diseases. As a consequence, there is a synergy between green nanotechnology and ZnO nanomaterials, which is leading to an exciting flourishment in the field, presenting a wide variety of biomedical applications of these nanostructures.

Green nanotechnology-based drug delivery systems for osteogenic disorders

February 2020

Expert Opinion on Drug Delivery

David Medina-Cruz

Ebrahim Mostafavi

Ada Vernet-Crua

Junjiang Cheng

Veer Shah

Jorge Luis Cholula-Diaz

Gregory Guisbiers

Juan Tao

José Miguel García-Martín

Thomas J Webster

Current treatments for osteogenic disorders are often successful, however they are not free of drawbacks, such as toxicity or side effects. Nanotechnology offers a platform for drug delivery in the treatment of bone disorders, which can overcome such limitations. Nevertheless, traditional synthesis of nanomaterials presents environmental and health concerns due to its production of toxic by-products, the need for extreme and harsh raw materials, and their lack of biocompatibility over time.

This review article contains an overview of the current status of treating osteogenic disorders employing green nanotechnological approaches, showing some of the latest advances in the application of green nanomaterials, as drug delivery carriers, for the effective treatment of osteogenic disorders.

Green nanotechnology, as a potential solution, is understood as the use of living organisms, biomolecules and environmentally friendly processes for the production of nanomaterials. Nanomaterials derived from bacterial cultures or biomolecules isolated from living organisms, such as carbohydrates, proteins, and nucleic acids, have been proven to be effective composites. These nanomaterials introduce enhancements in the treatment and prevention of osteogenic disorders, compared to physiochemically-synthesized nanostructures, specifically in terms of their improved cell attachment and proliferation, as well as their ability to prevent bacterial adhesion.

Naked Selenium Nanoparticles for Antibacterial and Anticancer Treatments

February 2020

ACS Omega

Luke D Geoffrion

Tina Hesabizadeh

David Medina-Cruz

Matthew Kusper

Patrick Taylor

Ada Vernet-Crua

Junjiang Chen

Alessandro Ajo

Thomas J Webster, Grégory Guisbiers

Currently, antibiotic resistance and cancer are two of the most important public health problems killing more than ∼1.5 million people annually, showing that antibiotics and current chemotherapeutics are not as effective as they were in the past. Nanotechnology is presented here as a potential solution. However, current protocols for the traditional physicochemical synthesis of nanomaterials are not free of environmental and social drawbacks, often involving the use of toxic catalysts. This article shows the production of pure naked selenium nanoparticles (SeNPs) by a novel green process called pulsed laser ablation in liquids (PLAL). After the first set of irradiations, another set was performed to reduce the size below 100 nm, which resulted in a colloidal solution of spherical SeNPs with two main populations having sizes around ∼80 and ∼10 nm. The particles after the second set of irradiations also showed higher colloidal stability. SeNPs showed a dose-dependent antibacterial effect toward both standard and antibiotic-resistant phenotypes of Gram-negative and Gram-positive bacteria at a range of concentrations between 0.05 and 25 ppm. Besides, the SeNPs showed a low cytotoxic effect when cultured with human dermal fibroblasts cells at a range of concentrations up to 1 ppm while showing an anticancer effect toward human melanoma and glioblastoma cells at the same concentration range. This article therefore introduces the possibility of using totally naked SeNPs synthesized by a new PLAL protocol as a novel and efficient nanoparticle fabrication process for biomedical applications.

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

April 2019

International Journal of Nanomedicine

Ada Vernet Crua

David Medina

Bohan Zhang

María Ujué González

Yves Huttel

José Miguel García-Martín

Jorge L Cholula-Díaz

Thomas J Webster

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. Here, tellurium (Te) nanowires were synthesized using a novel green chemistry approach, and their structures and cytocompatibility were evaluated. 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.

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

March 2019

International Journal of Nanomedicine

Diana Lomelí-Marroquín

David Medina Cruz

Alfonso Nieto-Argüello

Ada Vernet Crua

Junjiang Chen

Alejandro Torres-Castro

Thomas J Webster

Jorge L Cholula-Díaz

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.

Synergic antibacterial coatings combining titanium nanocolumns and tellurium nanorods

April 2019

Nanomedicine: Nanotechnology, Biology and Medicine

David Medina 

Maria Ujue Gonzalez

William Tien-Street

Marcial Fernandez-Vastro

Ada Vernet Crua

Ivan Fernandez-Martinez

Lidia Martinez

Yves Huttel

Thomas Webster

Jose Miguel Garcia Martin

Nanocolumnar titanium coatings have been fabricated in two sputtering systems with very different characteristics (a laboratory setup and semi-industrial equipment), thus possessing different morphologies (150 nm long columns tilted 20° from the normal and 300 nm long ones tilted 40°, respectively). These coatings exhibit similar antibacterial properties against Gram positive (Staphylococcus aureus) and Gram negative (Escherichia coli) bacteria. When a synergic route is followed and these coatings are functionalized with tellurium (Te) nanorods, the antibacterial properties are enhanced, especially for the long nanocolumns case. The biocompatibility is preserved in all the nanostructured coatings.

Citric juice-mediated synthesis of tellurium nanoparticles with antimicrobial and anticancer properties

March 2019

Green Chemistry

David Medina 

William Tien-Street

Bohan Zhang

Xinjing Huang

Ada Vernet Crua

Alfonso Nieto-Arguello

Jorge Luis Cholula-Diaz

Lidia Martinez

Yves Huttel

Marua Ujue Gonzalez

Jose Miguel Garcia-Martin

Thomas Webster

Bacterial infections and cancer are two of the most significant concerns that the current healthcare system should tackle nowadays. Green nanotechnology is presented as a feasible solution that is able to produce materials with significant anticancer and antibacterial activity, while overcoming the main limitations of traditional synthesis. In the present work, orange, lemon and lime extracts were used as both reducing and capping agents for the green synthesis of tellurium nanoparticles (TeNPs) using a microwave-assisted reaction. TeNPs showed a uniform size distribution, and rod- and cubic-shapes, and were extensively characterized in terms of morphology, structure and composition using TEM, SEM, XPS, XRD, FTIR and EDX analysis. TeNPs showed an important antibacterial activity against both Gram-negative and -positive bacteria in a range concentrations from 5 to 50 μg mL−1 over a 24-hour time period. Besides, nanoparticles showed an anticancer effect towards human melanoma cells over 48 hours at concentrations up to 50 μg mL−1. Moreover, the Te nanostructures showed no significant cytotoxic effect towards human dermal fibroblast at concentrations up to 50 μg mL−1. Therefore, we present an environmentally-friendly and cost-effective synthesis of TeNPs using only fruit juices and showing enhanced and desirable biomedical properties towards both infectious diseases and cancer.

Synthesis and characterization of PVP-coated tellurium nanorods and their antibacterial and anticancer properties

October 1, 2018

Journal of Nanoparticle Research

Christopher D. Brown

David Medina 

Amit K. Roy

Thomas Webster

Antibiotic resistance is a predicament that affects more than 2 million people worldwide each year. Through the over-prescription and extensive use of antibiotics, bacteria have generated resistance to many common antibiotic treatments. A promising approach to target antibiotic-resistant bacteria is the use of metallic nanoparticles. In this work, an environmentally safe synthesis of tellurium nanoparticles was explored. Rod-shaped tellurium nanoparticles coated with polyvinylpyrrolidone (PVP) were prepared using a facile hydrothermal reduction reaction. Transmission electron microscopy (TEM) images were used to characterize the size and morphology of the nanoparticles and showed a narrow size distribution. In addition, energy dispersive X-ray spectroscopy (EDS) was performed to verify the chemical composition of the nanoparticles. Antibacterial assays determined that treatment with nanoparticles at concentrations of 25 to 100 μg/mL induced a decay in the growth of both Gram-negative and Gram-positive bacteria—both antibiotic-resistant and non-antibiotic-resistance strains. To determine the effects of the nanoparticles on off-target cells, cytotoxicity assays were performed using human dermal fibroblasts (HDF) and melanoma (skin cancer) cells for durations of 24 and 48 h. Treatment with nanoparticles at concentrations between 10 and 100 μg/mL showed no significant cytotoxicity towards HDF cells. Contrarily, in melanoma cells, a cytotoxic effect was observed at the same concentrations. This suggests that the nanoparticles possess both anticancer properties towards melanoma cells and antibacterial effects without being toxic to healthy cells. These properties show that, for the first time, PVP-coated tellurium nanorods can be exploited for the treatment of antibiotic-resistant bacterial infections. These nanorods should be further explored for numerous antibacterial and anticancer applications.

Synthesis and Characterization of Biogenic Selenium Nanoparticles with Antimicrobial Properties Made by Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Pseudomonas aeruginosa


January 22, 2018

Journal of Biomedical Materials Research: Part A

David Medina

Guije Mi

Thomas Webster

Antimicrobial resistance is a global concern that affects more than 2 million people each year. Therefore, new approaches to kill bacteria are needed. One of the most promising methodologies may come from metallic nanoparticles, since bacteria may not develop a resistance to these nanostructures as they do for antibiotics. While metallic nanoparticle synthesis methods have been well studied, they are often accompanied by significant drawbacks such as cost, extreme processing conditions and toxic waste production since they use harsh chemicals such as corrosive agents (hydrazine) or strong acids (hydrochloride acid). In this work, we explored the environmentally safe synthesis of selenium nanoparticles, which have shown promise in killing bacteria. Using Escherichia coli, Pseudomonas aeruginosa, Methicillin-resistance Staphylococcus aureus (MRSA) and Staphylococcus aureus, 90-150 nm average diameter selenium nanoparticles were synthesized using an environmentally-safe approach. Nanoparticles were characterized using transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX) to determine the chemical composition, and ICP-MS to validate chemistry. Nanoparticles were also characterized and tested for their ability to inhibit bacterial growth. A decay in bacterial growth after 24 hours experiment was achieved against both Staphylococcus aureus and Escherichia coli at biogenic selenium nanoparticle concentrations from 25 to 250 µg/mL and showed no significant cytotoxicity effect against human dermal fibroblasts (HDF) cells for 24 hours. Bacteria were able to synthesize selenium nanoparticles through the use of different functional structures within the organisms, mainly enzymes such as selenite reductases. Therefore, biogenic selenium nanoparticles made by bacteria represent a viable approach to reduce bacteria growth without antibiotics overcoming the drawbacks of synthetic methods that employ toxic chemicals.

©2018