Florida State University Researchers take big step forward in nanotech-based drugs

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Florida State University Summary:New research takes a step forward in the understanding of nanoparticles and how they can best be used to deliver drugs.

Nanotechnology has become a growing part of medical research in recent years, with scientists feverishly working to see if tiny particles could revolutionize the world of drug delivery.

But many questions remain about how to effectively transport those particles and associated drugs to cells.

In an article published in Scientific Reports, FSU Associate Professor of Biological Science Steven Lenhert takes a step forward in the understanding of nanoparticles and how they can best be used to deliver drugs.

After conducting a series of experiments, Lenhert and his colleagues found that it may be possible to boost the efficacy of medicine entering target cells via a nanoparticle.

“We can enhance how cells take them up and make more drugs more potent,” Lenhert said.

Initially, Lenhert and his colleagues from the University of Toronto and the Karlsruhe Institute of Technology wanted to see what happened when they encapsulated silicon nanoparticles in liposomes — or small spherical sacs of molecules — and delivered them to HeLa cells, a standard cancer cell model.

The initial goal was to test the toxicity of silicon-based nanoparticles and get a better understanding of its biological activity.

Silicon is a non-toxic substance and has well-known optical properties that allow their nanostructures to appear fluorescent under an infrared camera, where tissue would be nearly transparent. Scientists believe it has enormous potential as a delivery agent for drugs as well as in medical imaging.

But there are still questions about how silicon behaves at such a small size.

“Nanoparticles change properties as they get smaller, so scientists want to understand the biological activity,” Lenhert said. “For example, how does shape and size affect toxicity?”

Scientists found that 10 out of 18 types of the particles, ranging from 1.5 nanometers to 6 nanometers, were significantly more toxic than crude mixtures of the material.

At first, scientists believed this could be a setback, but they then discovered the reason for the toxicity levels. The more toxic fragments also had enhanced cellular uptake. That information is more valuable long term, Lenhert said, because it means they could potentially alter nanoparticles to enhance the potency of a given therapeutic.

The work also paves the way for researchers to screen libraries of nanoparticles to see how cells react.

“This is an essential step toward the discovery of novel nanotechnology based therapeutics,” Lenhert said. “There’s big potential here for new therapeutics, but we need to be able to test everything first.”

Story Source:

Materials provided by Florida State University. Original written by Kathleen Haughney. Note: Content may be edited for style and length.

Journal Reference:

  1. Aubrey E. Kusi-Appiah, Melanie L. Mastronardi, Chenxi Qian, Kenneth K. Chen, Lida Ghazanfari, Plengchart Prommapan, Christian Kübel, Geoffrey A. Ozin, Steven Lenhert. Enhanced cellular uptake of size-separated lipophilic silicon nanoparticles. Scientific Reports, 2017; 7: 43731 DOI: 10.1038/srep43731


Florida State University: Promising nanomaterials origin revealed: “Building Nanomaterials from the Bottom-Up”

buckyballFlorida State University scientists are offering a new understanding of how an intriguing nanomaterial—metallofullerene—is formed in a recently published research study. 

Metallofullerenes are part of the carbon family, and kin to what’s popularly known as buckyballs. Buckyballs, or fullerenes, are hollow, soccer-ball-shaped, spherical cages that represent a basic form of carbon. The empty spaces in the fullerenes can trap , resulting in metallofullerenes.

“Metallofullerenes are a unique form of molecular nanocarbon,” says FSU chemist Paul Dunk, a co-author of the study. “They are potentially useful in a number of biomedical diagnostics, in particular as MRI contrast agents.”

The published findings could help pave the way for metallofullerene-based applications that range from biomedicine to renewable energy. The article, “Bottom-up formation of endohedral metallofullerenes is directed by charge transfer,” was published in the December issue of Nature Communications.

“Under certain conditions, metallofullerenes can have spectacular properties that make them prized as advanced materials for an array of technologies, such as conversion of sunlight into electricity and as possible components of molecular electronics,” Dunk said.Florida State U 54dcb7c6edea5

The metal-encapsulated carbon cages may even be important cosmic molecules, forming in stellar environments and stardust.

To discover how metallofullerenes are synthesized in a lab, the research team relied on the high magnetic field instrumentation available at the Ion Cyclotron Resonance facility at the National High Magnetic Field Laboratory. The international team included: Florida State’s Harry Kroto, recipient of the 1996 Nobel prize in chemistry for the discovery of fullerenes; MagLab chemists; and scientists from the University Rovira i Virgili in Spain and Nagoya University in Japan.

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Metallofullerenes are made by an astonishingly simple process: Mix graphite and a metal, and then vaporize it into soot, which looks like the black stuff from a candle flame. From that soot, metallofullerenes are mysteriously found.

“By vaporizing carbon and metal under the right conditions, these fascinating materials spontaneously assemble,” Dunk said. “But if the primary way in which they form is not even known, it’s difficult to figure out how to better produce these exciting molecules.”

While empty cages such as Buckminsterfullerene, C60, are available in ton quantity today, metallofullerenes suffer from limited quantities, thereby hindering research that fully explores the material.

“We first saw evidence for metallofullerenes just days after the discovery of Buckminsterfullerene in 1985, but we were not sure how they even formed. It was just amazing that they even did,” Kroto said. “That was nearly three decades ago. Despite major advances over the past 10 years, the formation process has proved very challenging because it occurs in a blink of an eye.”

To uncover the long-standing puzzle, researchers used a laser to blast graphite doped with metal, and the complex products formed were analyzed by the lab’s 9.4-tesla Fourier transform mass spectrometer. The powerful analysis technique allowed the team to meticulously study metallofullerene formation with a whopping 90 different elements, nearly all available elements of the periodic table.

The unprecedented results allowed the formation mechanism to be pieced together, building on recent pioneering work on empty cages from the same group.

Previously, it was predicted that flat sheets of carbon should be ejected from graphite and close up to form giant metallofullerenes, which could then hypothetically “shrink” into medium-sized cages that are most commonly used in biomedicine and technology.

However, the researchers observed an opposite outcome in their experiments. They found a metal atom initially nucleates carbon to form very small metallofullerenes, which then grow into the well-known larger cage sizes.

The type of metal encapsulated appeared to significantly affect how fast the small metallofullerenes grew into the most useful medium-sized cages, which could help explain the low yield of metallofullerenes by use of typical synthesis methods.

Clarification of the how molecular construction of these metal-encapsulated carbon cages occurs should help to open up new directions in nanotechonolgy.

“We hope these results will be useful in devising new production strategies to fully realize metallofullerene applications and further explore their amazing properties, which would certainly benefit society,” Dunk said.

Explore further: Molecular striptease explains Buckyballs in space

‘Butterfly’ molecule could build sensors, photoenergy devices

U of FLA Sensors bmaExciting new work by a Florida State University research team has led to a novel molecular system that can take your temperature, emit white light, and convert photon energy directly to mechanical motions.

And, the molecule looks like a butterfly.

Biwu Ma, associate professor in the Department of Chemical and Biomedical Engineering in the FAMU-FSU College of Engineering, created the molecule in a lab about a decade ago, but has continued to discover that his creation has many other unique capabilities.

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For example, the molecular butterfly can flap its “wings” and emit both blue and red light simultaneously in certain environments. This dual emission means it can create white light from a single molecule, something that usually takes several luminescent molecules to achieve.

And, it is extremely sensitive to temperature, which makes it a thermometer, registering temperature change by emission color.

“This work is about basic, fundamental science, but also about how we can use these unique findings in our everyday lives,” Ma said.

Among other things, Ma and his team are looking at creating noninvasive thermometers that can take better temperature readings on infants, and nanothermometers for intracellular temperature mapping in biological systems. They are also trying to create molecular machines that are operated simply by sunlight.

“These new molecules have shown very interesting properties with a variety of potential applications in emerging fields,” Ma said. “I have been thinking of working on them for quite a long time. It is so wonderful to be able to make things really happen with my new team here in Tallahassee.”

The findings are laid out in the latest edition of the academic journal Angewandte Chemie. Other authors for this publication are Mingu Han, Yu Tian, Zhao Yuan and Lei Zhu from the Chemistry and Biochemistry Department. Florida State has also filed a patent application on the work.

Ma came to Florida State in 2013 from the Lawrence Berkeley National Laboratory as part of a strategic push by the university to aggressively recruit and hire up-and-coming researchers in energy and materials science.

In addition to the faculty hires, the university has invested in top laboratory space and other resources needed to help researchers make technology breakthroughs.

“This type of research is why we continue to invest in materials science and recruit faculty like Biwu Ma to Florida State,” said Vice President for Research Gary K. Ostrander. “Making this area of research a priority shows why FSU is a preeminent institution, and we look forward to what Biwu and our other scientists can accomplish in the years to come.”