Controllable and sufficient concentrations
of therapeutic
agents
in gene therapy are critical to achieve satisfactory outcomes. Herein,
a Zn2+/Cu2+ bimetallic nano metal–organic
framework loaded with rolling circle amplification (RCA) substrates
(termed PZCT) was established for precise and efficient DNAzyme-based
gene and chemo-dynamic combined therapy. The activation of PZCT is
bioorthogonally controlled by tumor-specific miR-21, which generates
numerous DNAzyme for silencing EGR-1 mRNA with the assistance of Zn2+ from PZCT. Simultaneously, the doped copper ions on PZCT
exert chemo-dynamic therapy (CDT) by reducing glutathione (GSH) and
converting endogenous hydrogen peroxide (H2O2) into hydroxyl radical (·OH). These combination therapies exhibited
remarkable tumor elimination effects in vivo and
promised excellent tumor specificity via a bioorthogonal strategy.
The proposed nanoplatform offers new prospects for precise cancer
therapeutics by overcoming low transfection efficiency and off-target
toxicity in DNAzyme-based approaches.