Upconversion Luminescence-Boosted Escape of DNAzyme from Endosomes for Enhanced Gene-Silencing Efficacy.

Despite the enormous potential of DNAzyme for gene therapy, its efficacy is hampered by the limited endosomal escape capability. Here, we develop a near-infrared (NIR) light-controlled DNAzyme delivery platform to achieve enhanced gene-silencing efficacy. The nanoplatform is composed of therapeutic DNAzyme, photosensitizers (PSs) and upconversion nanoparticles (UCNPs) that can convert NIR light to visible light. The system allows NIR light-activatable generation of cytotoxic reactive oxygen species due to the energy transfer from the UCNPs to PSs, which boosts the endosomal escape of DNAzyme for an improved gene-silencing efficacy. We demonstrate that the nanocomposites represent a promising platform to integrate DNAzyme-based gene therapy with NIR light-triggered photodynamic therapy for combinational tumor treatment. This work highlights a robust approach to combat the current limitations of DNAzyme delivery systems.