Applications in Gene Therapy, Drug Delivery, and Artificial Cell Design Expected
From individual proteins to whole tissues, scientists have been engineering or growing biological mimics for a variety of medical and industrial applications. Bioengineers from the Institute for Medicine and Engineering (IME) at the University of Pennsylvania have designed an artificial capsule that imitates many of the qualities of natural cells. The capsule – dubbed a polymersome – has wide-ranging possibilities, from a new gene-therapy delivery vehicle to an artificial red blood cell. The collaborative study between IME and the University of Minnesota describes the physical properties of the capsules. The team’s findings appear in the May 14 issue of Science.
"We’ve created an entirely new type of synthetic capsule," says co-senior author Daniel Hammer, PhD, professor of chemical engineering. "The polymersomes are the same size as natural cells, but their outer membrane is much tougher than the phospholipid membrane of biological cells. And, they have the capacity to be undetectable by the human immune system so could be used to deliver all kinds of therapies to specific targets."
The capsules were produced using block copolymer chemistry. A carbon-based polymer and an organic solvent are dried on a wire. Then water is added to the system and the wire is zapped with electricity. Over time, as the polymer film lifts off the wire’s surface, capsules automatically form.
"Using this method we’ve been able to make capsules the size of natural cells from synthetic polymers, which has never been done before," notes Dennis Discher, PhD, co-senior author and assistant professor of mechanical, chemical, and bioengineering. The largest artificial cell made prior to these are a micron in diameter, whereas the polymersomes range from 10 to 35 microns. Most human cells are 10 microns.
Polymersomes are also biocompatible. A chemical tag made from polyethylene oxide is used to make lipid capsules and other biological delivery vehicles invisible to the immune system. The polymersomes have this polyethylene oxide tag built in. So far, the polymersomes are not recognizable by human immune cells in culture.
Because the polymersomes are the same size as human cells and are able to evade detection, they could be used to deliver all sorts of payloads to human tissues. One of the more general applications might be for an artificial blood supply. The polymersomes could be made to encapsulate one or more of the oxygen-carrying molecules found in the body. "These could be useful in any kind of trauma or crisis situation, or where there’s a question about disease transmission," notes Hammer. "And, more futuristically, an artificial supply might be useful in any kind of confined environment such as on a space station where you might want to store oxygen in ways that don’t involve compressed gas."
Polymersomes could also be used to ferry a package – such as an engineered gene or pharmaceutical — to a specific location in the body. The membranes would contain a chemical tag – much like the polyethylene oxide head – that is recognized by only certain cells. Once administered to a patient, the polymersomes would find their way to cells with a specific binding site for the chemical tag.
The team also found that the polymersomes are an order of magnitude tougher than other capsules that more closely resemble natural cells. This resiliency is important for any capsule that would experience repeated stress, for example when buffeted about in the human circulatory system. "The polymersomes can withstand fluid stresses in physiological solutions for up to a month without falling apart," says Discher.
Despite the desired toughness, the researchers say that because the polymersomes are made synthetically, they have wider control over the properties they can engineer. "For example, it is likely that we can make polymersomes that fall apart in response to ultrasound to release their contents," says Hammer.
Polymersomes also mimic the way biological cells change shape in response to environmental factors, such as density or temperature. This property makes the polymersomes a potentially good biological sensor: As the capsule changes shape and therefore optical properties, it can be tracked on its travels through a changing biological microenvironment, such as the kidney.
Coauthors on the paper are Bohdana Discher, David Ege, and James Lee from IME and Frank S. Bates and You-Yeon Won from the University of Minnesota.
Source: University Of Pennsylvania Medical Center. May 13,1999.