Nanotechnology is enabling new materials and devices that work at sizes so small that individual atoms and molecules make a difference in their behavior. The field is moving so fast, however, that scientists from other disciplines can have a hard time using the fruits of this research without becoming nanotechnologists themselves.

With that kind of technology transfer in mind, the University of Pennsylvania’s Center for Targeted Therapeutics and Translational Nanomedicine has established the Chemical and Nanoparticle Synthesis Core.

Supported by the Perelman School of Medicine and its Institute for Translational Medicine and Therapeutics, the School of Engineering and Applied Science, and the School of Arts & SciencesDepartment of Chemistry, this core facility aims to help Penn researchers design and synthesize custom molecules and nanoscale particles that would be otherwise hard to come by.

“Based on a short survey we conducted, we found that many faculty members want to synthesize unique chemical compounds, such as imaging agents, drugs or nanoparticles, but they don’t have the expertise to produce these compounds themselves,” says Andrew Tsourkas, professor in Penn Engineering’s Department of Bioengineering and Director of the Chemical and Nanoparticle Synthesis Core. “As a result, these projects are often abandoned.”

Claire Mitchell, professor in the School of Dental Medicine’s Department of Anatomy & Cell Biology and the Perelman School of Medicine’s Department of Physiology, knows this story all too well. As one of the Core Facility’s first users, she’s restarting neuroscience research that had been long stymied by a lack of access to nanotech expertise.

Six years ago, Mitchell began a research project that investigated the role of the lysosomes on aging-related diseases, such as macular degeneration and Alzheimer’s. The organelles responsible for degrading cellular waste, lysosomes become less acidic as people and their cells age, and thus less capable of breaking down this waste.

Mitchell collaborated with a colleague at the University of Colorado, who developed nanoparticles that lysosomes would ingest. The nanoparticles help the lysosomes acidify, which leads to the more efficient degradation of cellular waste. They published preliminary findings that suggested that preventing the accumulation of these waste products may help prevent early signs of macular degeneration in retinal cells.

Mitchell’s next target was neurons; while getting the nanoparticles to a patient’s brain would be an additional challenge, she hypothesized that in vitro studies that would show their pH-lowering effect would offer a new therapeutic approach for the treatment of Alzheimer’s.

However, after Mitchell’s initial supply of nanoparticles ran out, she was unable to procure any more.

“My colleagues and I have tried a dozen or more potential research collaborators, but for synthetic chemists, our nanoparticles just aren’t very interesting on their own,” Mitchell says. “While we recognized their considerable potential, the relative simplicity of these nanoparticles made them less interesting for the chemists; they weren’t worth their time or effort to make.”

The nanoparticles in question are simply microscopic balls of polylactic acid (PLA), a plastic that is commonly used as a medium for 3D printing. The trick was getting them to the exact diameter necessary for Mitchell’s experiments: 300 nanometers.

A uniform size is key, as it allows the nanoparticles to enter the lysosomes and reduces off-target effects. While Mitchell and her lab members had access to the equipment and materials to make PLA nanoparticles, they needed professional help to achieve the necessary level of precision.

“We tried to make these nanoparticles ourselves, but we’re not chemical synthesis experts,” Mitchell says. “The Core Facility is a dream come true. Not having to reinvent the wheel allows us to focus on our neuroscience and the prevention of age-dependent damage to the cells.”

Mitchell’s forthcoming experiments with the PLA nanoparticles will investigate the link between microglial cells and the amyloid plaques that are a hallmark of Alzheimer’s. Microglial cells are the primary phagocytes of the brain; she and her colleagues hypothesize that acidifying their lysosomes will improve their ability to clear these plaques.

“Once we’re back to where we were six years ago, there’s huge opportunities to tweak these nanoparticles for new experiments,” Mitchell says. “There are lots of ways we can improve the nanoparticles’ design to enhance and improve this approach. The whole lab is excited that the Core will help us finally make these nanoparticles. It’s a great lesson to never give up.”

Image: Nanoparticles enhanced the degradation of cellular waste in light-sensing retinal cells, according to research by Penn Dental Medicine’s Claire Mitchell, an activity that may help prevent early signs of macular degeneration. (Image Courtesy of PLOS One)

 

 

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