Synthesis of 'naked' tellurium dioxide nanoparticles for antimicrobial and anti-cancer applications

(Nanowerk Spotlight) The threat of resistance to antimicrobial agents has been growing at an alarming rate in recent years and poses a global health threat. Antimicrobial resistance occurs when pathogens (bacteria, viruses, fungi and parasites) change over time and no longer respond to medicines, consequently infections become increasingly difficult or impossible to treat. Especially worrisome are multidrug-resistant bacteria that have evolved resistance to several, if not all, antimicrobial agents.
Generally, the use of nanoparticles, either alone or in combination with other antibiotics, has proven to be an effective strategy to improve bacterial killing strategies. The challenge in synthesizing suitable nanoparticles is not only about controlling the size, the shape of the nanomaterial but also the chemical composition and the phase of the nanomaterial.
One such recent example is the demonstration of the effectiveness of tellurium dioxide (TeO2) nanoparticles against some antibiotic-resistant bacteria (such as multi-drug resistant E. coli and the deadly Methicillin-resistant S. aureus) and some types of cancer (such as skin cancer).
"The exciting result is that we need much less than 10 ppm to eradicate those deadly pathogens," Gregory Guisbiers, an Assistant Professor at the University of Arkansas at Little Rock, who led this study, tells Nanowerk. "The 'naked' nature of the nanoparticle surface helped to eradicate the antibiotic resistant bacteria at a very low concentration after just 8 hours of culture."
The findings are published in ACS Omega ("Synthesis of 'naked' TeO2 nanoparticles for biomedical applications").
By irradiating a pure tellurium target in deionized water, the researchers formed 'naked' tellurium dioxide nanoparticles with a spherical morphology and a size of around 70 nm. The surface of those nanoparticles is totally clean (hence 'naked'), meaning that it does not contain any residues from chemical reactions. This surface cleanliness makes them ideal to interact with biological pathogens.
Sketch showing the PLAL synthesis protocol for 'naked' tellurium dioxide nanoparticles
(a) Sketch showing the PLAL synthesis protocol. (b) Tyndall effect observed on the colloid synthesized by PLAL @ 1000 Hz. The left solution is the solvent, i.e. deionized water, while the right solution is the colloid containing the TeO2 nanoparticles. c) SEM image of the TeO2 nanoparticles contained in the colloid synthesized by PLAL @ 1000 Hz. d) EDX line scan through one TeO2 particle. (Note: Will get reprint permission once the DOI is live)
One of the earliest applications of TeO2 in biomedical applications came from its use as an antibiotic. In the pre-penicillin era, Te-based compounds were used by Alexander Fleming to inhibit the growth of many pathogens.
"Now that we are facing an increase in the resistance of those pathogens against the antibiotics we need to find new solutions," says Guisbiers. "So, what motivated me to conduct this work is that Te is absent from biological organisms on Earth, therefore Te-based compounds may unlock new mechanisms of action against deadly biological pathogens. Although tellurium itself is not particularly toxic, the absence of tellurium from the biological world may explain the efficacy of tellurium compounds such as TeO2 because pathogens didn't need to develop resistance against it."
"One of the most important factors impacting the applicability and activity of any nanoparticle is how they are made and the presence of synthetic by-products in their final form," explains Tina Hesabizadeh, a PhD student in Guisbier's group and the paper's first author. "Nowadays, TeO2 nanoparticles are synthesized by various techniques such as biosynthesis, spray pyrolysis, thermal evaporation, sonochemistry, and Pulsed Laser Ablation in Liquids (PLAL). Among these techniques, PLAL is the one that creates nanoparticles with a clean surface – i.e., without any surfactants or impurities attached – allowing them to interact efficiently with their environment. This advantage is particularly suitable for catalytic and antibacterial applications."
The novelty of this work is the use of a high repetition rate (1 kHz) pulsed laser (an infrared nanosecond pulsed laser emitting at 1064 nm) when irradiating a tellurium target – this PLAL synthesis technique is the first to demonstrate the ablation of a pure static Te target in the kHz regime.
"By increasing the repetition rate from 100 Hz to 1 kHz, we noticed an increase of 36% in the production rate of TeO2 nanoparticles during a 5-minute irradiation," Hesabizadeh notes. "This work also is the first time that TeO2 nanoparticles produced by PLAL are tested against antibiotic resistant bacteria such as multi-drug resistant Escherichia coli and Methicillin resistant Staphylococcus aureus as well as a cancer cell, specifically human melanoma cells."
The mechanism that makes the TeO2 nanoparticles toxic for pathogens is the incorporation of tellurium into sulfur-containing amino acids, such as cysteine and methionine, which are semi-essential and essential amino acids for bacteria function, respectively. These amino acids can consequently disrupt the metabolism of the bacteria.
The next step of the team's investigation will be to control the aspect ratio of the tellurium dioxide nanoparticles. Indeed, the morphology may also have some specific influence on the effectiveness of the nanoparticles against pathogens. This will be explored next.
"Scientists will become more attentive to the great potential of Te-based compounds such as tellurium dioxide in medicine," Guisbiers concludes. "UA Little Rock has already filed a provisional patent on this technology and we are looking to license the technology to start-up companies interested in our technology."
By Michael is author of three books by the Royal Society of Chemistry:
Nano-Society: Pushing the Boundaries of Technology,
Nanotechnology: The Future is Tiny, and
Nanoengineering: The Skills and Tools Making Technology Invisible
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