Taking a critical step toward the development of a multifunctional nanoscale anticancer agent that can detect cancer, treat it, and then report on the success or failure of that treatment, investigators at the University of Michigan have developed a nanoscale sensor of cell death.
This sensor is built on the same biocompatible polymeric dendrimer platform that this research team has already used to image and treat tumors.
Reporting their work in the journal Biomacromolecules, James Baker, Jr., M.D., and his colleagues described a novel approach for using dendrimers to detect apoptosis, programmed cell death triggered by anticancer agents. Baker, who first began developing dendrimers as multifunctional nanoscale imaging and drug delivery platforms as part of the National Cancer Institute’s Unconventional Innovations Program, leads one of the NCI’s Cancer Nanotechnology Platform Partnerships.
Most approaches to detect apoptosis rely on the human protein annexin V, which binds to a hidden cell membrane component revealed in the initial stages of apoptosis. Baker’s group took a different approach, looking for the appearance of a protein called caspase-3, an enzyme activated early in the apoptosis process. This enzyme cleaves the bond between two specific amino acids – valine and aspartic acid – and researchers have capitalized on this specificity to design fluorescence-based assays for caspase-3. These assays use a physical process called flourescence resonance energy transfer, or FRET, that generates a bright fluorescent signal only when a specific chemical bond breaks. In this case, flourescence appears only when caspase-3 breaks a valine-aspartic acid bond in a specially designed substrate for this enzyme.