The English Renaissance philosopher Francis Bacon once pointed out that the remedy can be worse than the disease. He was writing about politics, but his words also apply to certain therapies. The risk of such an undesirable outcome is one of the challenges that UConn chemist Jessica Rouge is tackling.
The truth of Bacon’s saying can be seen in the toll that otherwise effective treatments such as chemotherapy take on the patient because of unwanted side effects. A delicate balance must be struck for the drugs to kill the cancer cells without killing too many healthy cells. Rouge hopes to tip the scale in favor of the healthy cells with the use of nanoparticles.
“We want smarter technology that will take the drugs where we want them to go,” she says. “With better targeting abilities, these nanoparticles can correct diseases at the genetic level, and only in the cells we intend to target.”
The nanoparticles would look something like tiny capsules studded with different molecules, some of which seek out and tightly bind to their target cells or proteins. The nanoparticles could then act on their intended target and release the drug they have transported.
The aim is to develop new aptamers (oligonucleotide or peptide molecules that bind to a specific target molecule) that can aid the application of therapeutic oligonucleotides, in the form of DNA or RNA that can enter cells and repair over- or under-expressed protein levels. By using aptamers, the nanoparticles can hone in on and bind to specific proteins or cell receptors. The hope is that by using aptamers, only cells or proteins that are damaged or diseased would receive the drugs, leaving healthy, normal tissues untouched, and therefore greatly reducing side effects.
Rouge’s research team is also working on making sure the nanoparticles only release the drug at the right moment, using enzymes inside the cells they target.
With better targeting abilities, these nanoparticles can correct diseases at the genetic level, and only in the cells we intend to target. — Jessica Rouge
One tricky aspect of designing aptamers for nonoparticles is that they tend to be delicate and challenging to deliver. Aptamers work well on their own, but are not always compatible with nanomaterials. Rouge aims to make these two components compatible by developing new chemical attachment strategies.
“We are working to make aptamers and nanoparticles work together so they get to the right place,” Rouge says. “By using nanoparticles, we can deliver the therapies at timescales or to locations that are more appropriate.”
Nanoparticles may provide another opportunity for asthma patients.
Rouge is now collaborating with UConn Health immunologist Roger Thrall to develop a nanoparticle that will utilize aptamers to target and deliver an anti-inflammatory drug directly to lung cells in individuals suffering from asthma. These steroidal anti-inflammatory drugs can often have widespread and non-desirable off-target effects within the body; by using aptamers, the researchers will work on delivering drugs specifically to the lungs, preventing them from going elsewhere in the body.
Another project for Rouge’s group involves working with UConn mechanical engineer Ying Li to study lipid bilayers to better understand and improve the cellular uptake of nanoparticles.
As a new researcher at UConn, Rouge was originally worried it would take a long time to get students to join the group. The opposite has turned out to be that case. “If anything,” she says, “I’m looking at where am I going to put everybody?”
Clinical trials for nanoparticles are already starting to provide estimates that some could be on the market within the next five to seven years.
“Off-target effects are the biggest thing we are trying to avoid right now,” says Rouge, “just like with any drug.”
