The Royal Society of Chemistry’s Biomaterials Science journal.

Collaborative research by Mohamed Attia and Daniel Whitehead was featured on the cover of the Royal Society of Chemistry’s Biomaterials Science journal.
Image Credit: The Royal Society of Chemistry

CLEMSON, South Carolina – To solve a problem, sometimes it takes a new perspective, maybe even the ability to turn traditional methods upside down.

This was the approach taken by Clemson University postdoctoral researcher Mohamed Attia and his mentor Daniel Whitehead, both of the College of Science’s department of chemistry. Their collaborative research titled “In situ preparation of gold–polyester nanoparticles for biomedical imaging” was featured on the cover of the June 7, 2020 issue of the Royal Society of Chemistry’s Biomaterials Science journal.

“People have known for a long time that you can use gold nanoparticles for imaging applications,” said Attia, who was lead author on the paper. “The challenge has always been how you deliver the gold nanoparticles into a biological medium so that they can be used for imaging. There have been a lot of different strategies that researchers have tried before, such as making the gold nanoparticles and then coating them with another material to allow them to access cells or biological tissues. What we did instead was to essentially reverse the order of things.”

Biomedical imaging applications can be used for the diagnosis of diseases such as cancer, developing strategies for personalized medicine, and monitoring of medical implants.

“We made polymeric nanoparticles that were known for a long time to easily interact with cells in biological settings,” said Whitehead, an associate professor who focuses on synthetic organic chemistry. “We took those polymeric nanoparticles and encapsulated the ingredients that you would need to make gold nanoparticles. We took the polymeric nanoparticles containing the reagents needed to generate gold nanoparticles and put them in the presence of cells. By irradiating these nanoparticles with UV light, the reaction will take place inside of the nanoparticles and make the gold nanoparticles for imaging right in the presence of the cells where you need them.”

Jeffrey Anker, professor in Clemson’s department of chemistry; Clemson postdoctoral researcher Meenakshi Ranasinghe; Frank Alexis, professor/vice chancellor at Yachay Tech University in Ecuador; and Roman Akasov of Sechenov First Moscow State Medical University in Russia rounded out the team.

Heads shots of Mohamed Attia, left, and Daniel Whitehead.

Mohamed Attia, left, and Daniel Whitehead.

The one-step synthesis marks a breakthrough because, unlike conventional methods, it synthesizes the imaging agent in situ.

“That’s what’s different about this approach compared to others,” Whitehead said. “We can actually generate the gold nanoparticles right in the presence of the cells, right when we want to use them.”

The research is a first step and proof of concept of what could one day be applied in the clinic for biomedical imaging.

“This paper describes the idea and demonstrates that we can encapsulate the reagents that you need to make gold nanoparticles inside of polymeric nanoparticles and then generate gold nanoparticles using light radiation,” Whitehead said.

Attia said the research showed that the gold nanoparticles could be completely formed in situ without causing cell toxicity, another critical factor for future practical use in medical imaging.

“The process of generating the gold nanoparticles in vitro did not kill the cells at all,” Attia said.

Images of cells

These cellular uptake images were captured by confocal microscopy of glioblastoma U-87 MG cells incubated for 24 hours with 500 µg/mL of synthesized gold nanoparticles.
Image Credit: Roman Akasov

While this research is preliminary, the potential of targeting and tracking specific cells and tissues is encouraging.

“The exciting part to me for future applications in the short term is that the polymeric nanoparticles that we are using to carry the ingredients to generate gold nanoparticles can be modified with different targeting elements on their surface,” Whitehead said. “So, we could actually take that carrier for the reagents of the gold nanoparticles and append to it targeting elements that would send it to particular tissues or cell types in the body.”

Whitehead said this research answered simple but necessary questions that lay the foundation for future study and ultimately, a potential path to exciting innovations.

“If we appropriately modify the polymer nanoparticles to carry the reagents for the gold with a targeting element that encourages those to localize only in cancer cells, then we can irradiate that site and then actually see only the imaging of the tumor cells, for instance,” Whitehead said.

“It may also be possible to encapsulate a drug in the formulation to generate a ‘theronostic’ material that serves as an imaging agent and a therapeutic simultaneously,” Attia concluded.