Boston’s newest pharmaceutical factories may be difficult to spot. Swimming inside the body, these tiny structures — a human cell is 1,000 times bigger — are built from fatty membranes, DNA, and enzymes.
In a study published this spring in Nano Letters, researchers at the Massachusetts Institute of Technology reported developing injectable nanoscale particles containing all the biological equipment needed to produce proteins. A flash of ultraviolet light on the skin switches on these self-contained factories, which lie just below the surface and can be engineered to make different molecules. With further development, the technique could one day help scientists produce and control drugs for cancer and other diseases right inside patients’ bodies.
“It’s very cool,” said James Heath, a chemist and cancer researcher at the California Institute of Technology in Pasadena, who was not involved in the study. “This looks a little bit like science fiction, but it’s actual science.”
Protein-based drugs represent a growing class of pharmaceuticals, especially for treating cancer, but they have short shelf lives and can be difficult to administer. Natural enzymes in the body are designed to break down proteins and in the process disable some drug molecules before they reach their target. The new nanoparticles can carry protein building blocks sheathed inside a protective outer membrane, assembling the final product only when the light is applied.
“This is a way to make small amounts of the protein at your therapeutic site,” said the MIT biomedical engineer, Daniel Anderson, who supervised the research.
The reaction starts when light penetrates a nanoparticle, breaking a molecular lock scientists installed to shield the DNA coding for a specific protein — in this case, a fluorescent indicator. Once researchers unlock the genes, helper molecules inside the particle begin to read the code and manufacture the protein. In the future, researchers say, nanoparticles might be engineered to produce a variety of proteins, including cancer drugs.
The project offers exciting possibilities for personalized medicine, said Avi Schroeder, lead author of the study and a postdoctoral researcher in the labs of Anderson and Robert Langer.
Patients who might benefit most from slightly different versions of the same drug could receive precisely tailored treatments.
“You can actually encode a specific protein per each patient, if you know what the patient needs,” Schroeder said.
Applying light specifically to diseased tissues could also help limit side effects of some drugs. Many existing cancer treatments work by poisoning dangerous cells, but they often damage healthy tissue in the process.
By locking the DNA, the scientists hope to contain the collateral damage.
“Even if these particles actually disperse in the entire body, you could turn them on only where you want them to be activated,” Schroeder said.
That type of specificity has excited other researchers at MIT, including neuroscientist Edward Boyden, who sees the nanoparticles as a potential research tool.
He envisions sending proteins to selected groups of neurons to change their behavior. However, “as with any new technology, it would be great to know how long it lasts, how specific it is, and what side effects there are,” said Boyden, who was notinvolved in part of the study.
In large amounts, ultraviolet radiation can cause serious side effects, including tissue damage and cancer. The researchers managed to stimulate protein production in mice with brief pulses lasting a few milliseconds — probably too brief to cause harm, Schroeder said.
A bigger concern is the limited range of ultraviolet light, which does not penetrate deep into the body. The technology might initially be more useful for treating conditions such as skin cancer, rather than pancreatic cancer, for example.
The team is interested in developing DNA locks that respond to other types of energy — that could include other wavelengths of light or even radio waves — to possibly reach different or deeper parts of the body.
Currently, no efforts are being made to commercialize the ultraviolet-triggered protein minifactories.
“This is early,” Anderson said. “I would say this is more of an academic discovery.”
If subsequent experiments succeed, commercial developments might soon follow.
Robert Langer, one of the senior authors of the study, has issued nearly 400 patents worldwide and has another 412 pending. Langer also founded the Cambridge start-up BIND Biosciences Inc., which reported in April early results of a drug-laden nanoparticle capable of identifying and invading tumors.
“This group is good at taking science fiction into science, then into actual applications, so I wouldn’t bet against them,” Heath said.