A Metal Ion-Controlled Molecular "Open Bridge" Detecting Oxidative Stress-Disrupted Apoptotic Signaling in Pediatric...

Neuroblastoma is a metastatic tumor almost exclusively plaguing young children. To provide an early warning for timely medical interference that may prevent such tragedies from happening, we mimic the biomolecular pathology of this disease and have obtained an assay without using costly biomolecules such as antibodies and enzymes but can still sensitively detect trace level metal ions and metastatic marker proteins in the cerebrospinal fluid of neuroblastoma-bearing children in a one-step and reagentless fashion. Specifically, a surface-tethered "open bridge"-like molecular machine is designed. This probe, after interacting with cupric ions, can form an electrochemically active peroxidase-like artificial enzyme. Its activity first opens the probe, freeing the Bcl-2-targeting sequence of the probe to adopt the most favorable conformation, forming a noncovalent complex with Bcl-2. Then, the peroxidase-like activity of the probe induces the formation a robust fluorescence covalent linkage with the target protein. This fluorescence and electrochemical dual detection allows an analytical performance not inferior to the commercially available methods, pointing to possible clinical application in the early screening of pediatric metastatic conditions in the near future.