期刊
ULTRASONICS SONOCHEMISTRY
卷 92, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ultsonch.2022.106262
关键词
siRNA; Nanoassembly; Cytosolic delivery; Gene therapy; Sonodynamic therapy
This study developed a sono-controllable strategy for effective cytoplasmic delivery of siRNAs in cancer gene therapy. A hybrid nano-assembly (HNA) was prepared, which generated singlet oxygen to facilitate the escape of siRNA from the lysosome to the cytoplasm. The combination of sono-gene therapy achieved a high cell death rate of 82%.
Cancer gene therapy by small-interfering RNAs (siRNAs) holds great promise but is impeded by a low cyto-plasmic delivery efficiency. The past two decades have witnessed many efforts that are dedicated to discover biomaterials in order to increase cellular uptake efficiency of siRNAs. However, less attention has been paid to the lysosomal trapping dilemma that greatly restricts gene silencing outcomes. Herein, to address this challenge, we developed a sono-controllable strategy for ultrasound-promoted cytosolic siRNA delivery. A hybrid nano -assembly (HNA) was prepared via electrostatic self-assembly of a siRNA and a nona-arginine modified with protoporphyrin IX that is a sonosensitizer. After cellular uptake and exposure to sono-irradiation, HNA generated singlet oxygen to facilitate the lysosomal escape of siRNA to knock down anti-apoptotic Bcl-2 in the cytoplasm. We showed that the colocalization ratios between siRNA and the lysosome decreased from 91 % to 33 % post sono-irradiation; meanwhile, the gene silencing efficacy increased from 46 % to 68 % at 300 nM of HNA. Furthermore, sonodynamic therapy was achieved by the sonosensitizer under ultrasound irradiation, which combined gene therapy to eradicate cancer cells, resulting in a cell death rate of 82 %. This study thus presents a novel ultrasonic approach for effective cytoplasmic delivery of siRNAs and combinational sono-gene therapy of cancer.
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