New design guide could advance development of nanomaterials detecting diseases

Scientists have long sought to develop drug therapies that can effectively diagnose, target and treat life-threatening diseases such as cancer, cardiovascular and autoimmune diseases. A promising approach is the design of circulating nanomaterials that can circulate in the body and provide diagnostic information or to release targeted drugs in response to disease marker enzymes. A recent article by researchers at the Advanced Science Research Center (ASRC) at New York City University's Graduate Center, Brooklyn College, and Hunter College shows that scientists now have design tips likely to rapidly advance the development of such nanomaterials.

In the paper, which appears online in the newspaper ACS Nano, the researchers detail the widely applicable results of their work to characterize a nanomaterial that can react predictably, specifically and safely when it detects overexpression of the matrix enzyme metalloproteinase-9 (MMP-9). MMP-9 helps the body break down unnecessary extracellular material, but when levels are too high, it plays a role in the development of cancer and many other diseases.

"At the present time, there are no clear rules on how to optimize nanomaterials so that they respond predictably to MMP-9," Jiye said. His, lead author of the study and PhD student at the Graduate Center. student working in one of the laboratories of the ASRC Nanoscience Initiative. "Our work describes an approach using short peptides to create enzyme-sensitive nanostructures that can be customized to take specific therapeutic actions, such as targeting only tumor cells and activating the release of drugs near these cells."

Methodology

The researchers designed a modular peptide that spontaneously badembles into nanostructures and is predictably and reliably transformed or broken down into amino acids on contact with the MMP-9 enzyme. The designed components include a charged segment of the nanostructure to facilitate its detection and engagement with the enzyme; a segment of the structure that can be cleaved so that it can block on the enzyme and determine how to respond to it; and a hydrophobic segment of the structure to facilitate self-badembly of the therapeutic response.

Importance

"These works are a crucial step in the creation of new smart drug delivery vehicles and diagnostic methods with precisely adjustable properties, which could change the treatment and management of diseases," said Rein Ulijn, Director of the CBCN's Nanoscience Initiative, whose lab directs the work. "While we have focused specifically on creating nanomaterials that can detect and respond to MMP-9, the components of our design guide can facilitate the development of nanomaterials that can detect and respond to others. cellular stimuli. "

Among the other advances, the work of the research team builds on their previous findings, which showed that amino acid peptides can encapsulate and transform into fibrous drug depots. when interacting with the MMP-9. The group is working with scientists from Memorial Sloan Kettering and Brooklyn College to use their findings to create a new cancer treatment.