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Programmable Nanoscale Drug Capsules Designed

Jessica Rouge

Jessica Rouge talks with Ph.D. student Josh Santiana (Sean Flynn, UConn Photo)

5 December 2017. A lab at University of Connecticut is developing nanoscale capsules that release drug cargoes only when encountering specific enzymes, even inside cells. The team led UConn chemistry professor Jessica Rouge describes its technology and results of lab tests in the 30 November issue of the journal Bioconjugate Chemistry (paid subscription required).

Rouge and colleagues are seeking more accurate delivery of drugs to specific targets, down to genetic material such as DNA or RNA inside cells. Not only can more accurate targeting of drugs deliver higher doses of compounds that kill cancer cells, but also spare healthy cells and tissue, thus reducing adverse side effects, like those experienced by cancer patients receiving chemotherapy.

The UConn researchers are developing a technology they call a nucleic acid nanoscale capsule — 1 nanometer equals 1 billionth of a meter — that uses cross-linking, a chemical method for bonding to proteins and other biological molecules. In this case, the team combines peptides with nucleic acids from DNA or RNA, which would release the drugs only in the presence of a specific enzyme. When the nano-capsule encounters that enzyme, it causes the capsule to degrade and release its contents.

The team tested the nano-capsules in lab and cell cultures with two different enzymes: cathepsin B found inside cells and associated with some cancers and inflammation, and matrix metallopeptidase 9 or MMP9 involved in the breakdown of extracellular matrices outside cells. The researchers found their nano-capsules would degrade when in the presence of these target enzymes, but remain intact in other environments. The team also found the nano-capsules could be made to remain intact in enzyme solutions with pH levels below certain thresholds, then degrade when exceeding that pH level.

“There’s no one-size-fits-all delivery system,” says Rouge in a university statement. “The beauty of this system is that it is programmable, modular, and has the ability to rapidly integrate diverse peptide sequences. It can be tailored to combat new disease challenges as they emerge.”

UConn says Rouge’s team in Storrs is working with other university labs to design drug-delivery mechanisms that treat various diseases, including inherited disorders requiring genetic therapies. One of those collaborators is Steven Szczepanek, who studies disease pathology and vaccines, and with whom Rouge is investigating a method for delivering drugs that silence genes producing proteins associated with inflammation in asthma.

The researchers plan to test their process soon in mice induced with asthma. The university says a patent is pending on the technology, and industry partners are being solicited to take the process to market.

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