Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 61, Issue 34, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202206485
Keywords
DNAzyme; Endosomal Escape; Gene Therapy; Photodynamic Therapy; Upconversion Nanoparticles
Categories
Funding
- Beijing Natural Science Foundation [JQ20005]
- National Natural Science Foundation of China [22005074]
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This study develops a near-infrared light-controlled DNAzyme delivery platform, which enhances the gene-silencing efficacy by improving the endosomal escape capability. The nanoplatform integrates DNAzyme-based gene therapy with NIR light-triggered photodynamic therapy for combinational tumor treatment.
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.
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