Researchers at the University of Aarhus, in Denmark, have taken such an approach to develop nanocarriers that can be triggered to deliver genes to diseased tissues.
Reporting its work in the journal Small, a team of investigators led by Kenneth Howard, Ph.D., and Flemming Besenbacher, Ph.D., described how they developed a temperature-sensitive polymer capable of complexing with DNA and forming nanorods that are stable at body temperature, or 37?°C. However, when heated to 42?°C, these rods expand dramatically, becoming too large to pass into or out of blood vessels. The researchers note that localized heating could be used to trap these nanorods in tumors, in essence creating a new way of targeting a drug delivery agent to tumors.
When exposed to the unique physiological conditions found inside tumors, these nanorods display another useful characteristic “ they fall apart. The researchers believe that this disassembly is thorough enough that the polymer no longer complexes at all with the DNA cargo. Electron microscopy studies appear to confirm this finding, suggesting that these nanorods could indeed deliver therapeutic genes into cancer cells.
This work is detailed in a paper titled, Nanocarrier stimuli-activated gene delivery. Investigators from Wayne State University also participated in this study. An abstract of this paper is available at the journal ™s website. View abstract.
nanoncer
Other researchers have suggested nerve cells also must be flexible to survive the process of wiring the nervous system. As a neuron grows, it sends out a "growth cone" which pulls the growing axon behind it. The axon must be able to withstand stretching.
How it does that has been a mystery - until now.
In the new study, the Utah biologists used mutant nematode worms lacking beta spectrin. The study focused on how the protein's absence affected axons, which carry nerve signals away from the nerve cell "body" and toward the synapse - the junction with another nerve cell.
The researchers used microscopes to photograph nerve-cell axons by inserting a jellyfish gene into the worms to make the worms' neurons glow fluorescent green.
The biologists found breaks as well as branching or inappropriate new growth cones - signs of nerve-repair attempts - in places where a nerve cell body sent an axon from one side of the worm to the other, making the axon and any damage easy to see.
The neurons were examined at three stages: as embryos, just after the worms hatched and at one day of age. The worms and their nerve cells still were growing during the first two stages.
In worm embryos, only 3 percent of nerve cells were broken or defective, despite the lack of beta spectrin. But in newly hatched mutant worms, 26 percent of nerve cells were broken or defective, and the percentage rose to 60 percent in day-old mutant worms.
Because the nerves did not break in younger worms, beta spectrin is not required for normal nerve growth and development, but is needed for preventing breakage of mature neurons, Hammarlund says.
In another experiment, the biologists paralyzed the worms by disabling two genes needed for muscles to contract. "In paralyzed worms, the axons do not break, even in the absence of spectrin, which says it is movement that causes the nerve cells to break, rather than continued growth of the animal," Jorgensen says.
That means beta spectrin normally prevents breakage by protecting neurons from the strain of movement, and not by helping add new membrane to a growing nerve cell.
Bastiani calls it amazing that disease-causing nerve-cell damage may come in the form of broken axons - the simplest part of a nerve cell. "Everybody focuses on the synapse or the cell body as to where the action is," he says. "But if you break the wire or axon, the neuron doesn't work anymore. It's sort of the weakest link in the process."
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