Cathepsin B‑Activated Prodrug for Precision Tumor Theranostics

In response to the systemic toxicity associated with
chemotherapeutic
agents and the diverse characteristics of the tumor microenvironment,
we present an innovative theranostic prodrug system, designated NM-001. NM-001 specifically targets the overexpressed
integrin ανβ3 on tumor cells
via the cRGD peptide, facilitating internalization into lysosomes.
Subsequently, cathepsin B selectively cleaves the GFLG peptide, triggering
an intramolecular self-elimination reaction that generates NM-002 with near-infrared (NIR) emission and releases chlorambucil (CLB).
Concurrently, the fluorescence property undergoes a transition from
green to NIR emission, enabling precise monitoring of the drug delivery
and release process, thereby establishing a dual-channel optical feedback
mechanism. This mechanism allows for real-time, in situ differentiation
of drug delivery and release dynamics at the cellular level. Both
in vitro and in vivo studies have demonstrated that NM-001 exhibits high selectivity and substantial antitumor efficacy against
tumor cells, presenting a promising novel approach for personalized
diagnosis and therapy.