Amplified Drug Delivery System with a Pair of Master Keys Triggering Precise Drug Release for Chemo-Photothermal Therapy

A versatile drug delivery system (DDS) enabling highly effective and targeting oncotherapy has always been of great significance in medical research. In the development of a stimuli-responsive DDS, compared with a single-factor stimulation DDS, a multifactor activation DDS has higher therapeutic specificity between diseased and normal tissue, but there are challenges in drug-release efficiency and united targeting cancer therapy. Herein, a novel dual-microRNA (dual-miRNA)-mediated 1:N-amplified DDS is fabricated. The gold nanocage (AuNC) was synthesized and used as a carrier. A DNA bridge motif as a nanolock (DNA bridge nanolock) was designed and modified on the surface of AuNCs, which could seal the holes of AuNCs. Using the dual-miRNAs as a pair of master keys, through DNA strand migration and DNAzyme self-assembly, a cell endogenous substance Mg2+-dependent DNAzyme cyclic shear reaction could perform the function of the master keys to open multiple locks for the enhanced release of doxorubicin from the AuNCs. In addition, under near-infrared irradiation, via absorption of light and heat release, the AuNC is activated to perform the function of photothermal therapy. Thereby, the system achieves precise chemo-photothermal therapy. Using the in vitro and in vivo anti-tumor analysis, the DDS could be proved to present a novel design of enhanced and targeted drug-release system for highly effective cancer therapy.