Tumor microenvironment-based smart beacon drug delivery system for in situ visualization of tumor therapy

Real-time monitoring of the effectiveness of tumor-targeted drugs is crucial for assessing their impact. To address this need, we developed a beacon drug delivery system, MDB, which incorporates tumor targeting, anti-tumor effects, and near-infrared fluorescence emission for on-site visualization of tumor therapy. In non-cancerous cells, MDB remains inactive as a prodrug but is selectively activated within tumor cells when the borate ester group reacts with H2O2 in the tumor microenvironment (TME), releasing the beacon drug MDBRe. MDBRe can down-regulate the expression of the protein heme oxygenase 1 (HO-1), ultimately disrupting the mitochondrial energy supply system and leading to tumor cell death. It also emits near-infrared fluorescence for drug tracking under structured illumination microscopy (SIM). Both in vitro and in vivo experiments confirm the effective delivery of MDBRe by MDB to H2O2-enriched tumor tissues, resulting in a potent anti-tumor effect, visualization of drug distribution in tumors, and monitoring of therapy progress. In conclusion, our approach presents a novel method for targeted drug delivery to tumors and enables real-time visual monitoring of the treatment process.