Scientists have created a drug delivery system that uses a synthetic-biological hybrid nanocapsule for targeted treatment of disease. If effective, they believe this could improve drug delivery and decrease side effects of drugs that target cancer and other diseases. Their research was published last week in Bioconjugate Chemistry.
"There's no one-size-fits-all delivery system," says Jessica Rouge, assistant professor of chemistry at UConn, and author of a new paper on the technology in Bioconjugate Chemistry. "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."
The platform combines synthetic peptides, surfacants, and nucleic acids to form a nanocapsule that can alter diseased cells at the genetic level. To do this, Rouge had to develop a new linker technology to link the synthetic drug delivery vehicle with a new peptide cross-linker approach. Both small molecules and biologics can be delivered with this system. Once the materials are guided to their target, they only release their contents if a specific enzyme triggers the peptide cross-linker.
The system was tested using two trigger enzymes commonly associated with malignancy in cells, cathespin B and MMP9. The nanocapsules successfully released their cargo only when treated with these enzymes and had no reaction to non-target enzymes with similar structures. The targeted nature of this system offers hope for reducing adverse side effects of cancer treatments.
Along with cancer treatment applications, the team is working to develop this system for other challenging disorders that don't currently have effective treatment options, including optical neuropathies and asthma.
Image: Enzyme-triggered degradation of a drug loaded peptide-crosslinked nucleic acid nanocapsule. First a peptide is crosslinked at the nanoparticle surface (1), then an enzyme recognizes the peptide crosslinker (2), and finally the enzyme cleavage leads to the release of the drug and any intact DNA (3). Image source: Artwork by Joseph Luciani/UConn.