A smart multiantenna gene theranostic system based on the programmed assembly of hypoxia-related siRNAs
| Autor: | Xiaoqing Liu, Ruomeng Li, Kaiyue Tan, Jie Wei, Chen Hong, Jing Liu, Haizhou Wang, Fuan Wang, Jinhua Shang, Xue Gong, Jing Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Small interfering RNA
Cell Survival Science General Physics and Astronomy 02 engineering and technology Computational biology Biology 010402 general chemistry 01 natural sciences Extracellular vesicles General Biochemistry Genetics and Molecular Biology Article Extracellular Vesicles Mice Targeted therapies RNA interference Cell Line Tumor microRNA Biomarkers Tumor Animals Humans Prodrugs Gene Silencing Precision Medicine RNA Small Interfering Hypoxia Gene Drug Carriers Multidisciplinary fungi General Chemistry Neoplasms Experimental 021001 nanoscience & nanotechnology 0104 chemical sciences siRNAs MicroRNAs DNA and RNA RNAi Drug delivery RNA Interference 0210 nano-technology |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | The systemic therapeutic utilisation of RNA interference (RNAi) is limited by the non-specific off-target effects, which can have severe adverse impacts in clinical applications. The accurate use of RNAi requires tumour-specific on-demand conditional activation to eliminate the off-target effects of RNAi, for which conventional RNAi systems cannot be used. Herein, a tumourous biomarker-activated RNAi platform is achieved through the careful design of RNAi prodrugs in extracellular vesicles (EVs) with cancer-specific recognition/activation features. These RNAi prodrugs are assembled by splitting and reconstituting the principal siRNAs into a hybridisation chain reaction (HCR) amplification machine. EVs facilitate the specific and efficient internalisation of RNAi prodrugs into target tumour cells, where endogenous microRNAs (miRNAs) promote immediate and autonomous HCR-amplified RNAi activation to simultaneously silence multiantenna hypoxia-related genes. With multiple guaranteed cancer recognition and synergistic therapy features, the miRNA-initiated HCR-promoted RNAi cascade holds great promise for personalised theranostics that enable reliable diagnosis and programmable on-demand therapy. The therapeutic application of small interfering RNA (siRNA) is challenging due to its non-specific targeting and delivery issues. Here, the authors report an endogenous micro-RNA guided and hybridisation chain reaction-promoted siRNA delivery system encapsulated in tumour-derived extracellular vesicles, with cancer-specific activation, and achieve silencing of hypoxia-related genes. |
| Databáze: | OpenAIRE |
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