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

摘要

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 photo-dynamic therapy for combinational tumor treatment.This work highlights a robust approach to combat the current limitations of DNAzyme delivery systems.