Researchers have demonstrated that a process using nanotechnology combined with mass spectrometric analysis can assess whether cancer drugs hit their targets, which may help reduce drug side effects, according to a study published online March 31 in Agnewandte Chemie International Edition.
Drug-conjugated dendrimers were used in combination with mass spectrometric analysis to identify drug targets in vitro and in living cells in the study conducted by W. Andy Tao, PhD, associate professor of analytical chemistry and chemical biology, Purdue University, West Lafayette, Ind. and colleagues.
In the study, the drug-conjugated nanopolymer was incubated with cells to ensure efficient delivery, and the cells were then lysed. In addition to the drug, the synthetic nanopolymer was equipped with a chemical group that was reactive to small beads. The beads retrieved the nanopolymer and any attached proteins after the drug had done its work. Proteins bound to the drug were isolated on a solid support and identified by mass spectrometry.
Tao believes that nanopolymers could better deliver drugs to their targets. Since they are nanosized and water soluble, the nanopolymers could gain access to cells more effectively than a standalone drug that is only minimally water soluble.
In addition, knowing which proteins are targeted would allow drug developers to test whether new drugs target only desired proteins or others as well. Eliminating unintended protein targets could reduce the often serious side effects associated with cancer drugs, according to Tao and colleagues.
The researchers demonstrated the nanopolymer's abilities using human cancer cells and the cancer drug methotrexate. The nanopolymers were tracked using a fluorescent dye to show they were entering cells. Tao and colleagues plan to use drugs that are based on synthetic peptides, which are larger, more specific and associated with fewer side effects in future studies.
The National Institutes of Health's National Center for Research Resources and a National Science Foundation Career Grant funded the research.