TY - JOUR
T1 - Upconversion Luminescence-Boosted Escape of DNAzyme from Endosomes for Enhanced Gene-Silencing Efficacy
AU - Chen, Yaoxuan
AU - Zhao, Rupeng
AU - Li, Lele
AU - Zhao, Yuliang
N1 - Funding Information:
This work was financially funded by the Beijing Natural Science Foundation (JQ20005) and the National Natural Science Foundation of China (22005074).
Publisher Copyright:
© 2022 Wiley-VCH GmbH.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - DNAzyme
KW - Endosomal Escape
KW - Gene Therapy
KW - Photodynamic Therapy
KW - Upconversion Nanoparticles
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U2 - 10.1002/anie.202206485
DO - 10.1002/anie.202206485
M3 - Article
C2 - 35730643
AN - SCOPUS:85134080103
SN - 1433-7851
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
ER -