An Azoreductase-Activated Self-monitoring Prodrug for Chemiluminescence Imaging and Safe Chemotherapy Breast Cancer

Theranostic prodrugs predominantly rely on fluorogenic
responses
to convey diagnostic signals during chemotherapeutic activation. While
chemiluminescence (CL) detection offers superior signal-to-noise
ratios over fluorescence, the utilization of Schaap’s as a
module in diagnostic prodrugs remains underexplored, limiting advancements
in this field. Herein, we present the first Azoreductase (AZR)-activated self-reporting theranostic prodrug utilizing a CL feedback mechanism. This prodrug has azo (-N = N-) bonds,
which can serve as an AZR recognition site and link the
melphalan analogue and Schaap’s scaffold. Under hypoxic tumor
conditions, AZR-mediated reduction of azobenzene triggers
prodrug cleavage, releasing the active drug and CL signal.
The AZR-selective activation can facilitate tumor-specific
therapeutic effects, thus enabling precision chemotherapy. Our study
has confirmed that Schaap’s CL platform, activated
by AZR, is a promising strategy for integrating real-time
diagnostic imaging with controllable treatment. These findings advance
the development of CL-based theranostic agents for safe
and effective breast cancer treatment.