Dual-targeted siRubicon delivery strategy triggers hepatocellular lipophagy for mitigating liver steatosis
Abstract Metabolic dysfunction-associated steatotic liver disease is marked by fat accumulation and inflammation, partly due to impaired lipophagy—a cellular process in which lipid droplets are broken down through autophagy. Rubicon, a protein that inhibits this process, worsens the condition by blo...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61965-x |
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| Summary: | Abstract Metabolic dysfunction-associated steatotic liver disease is marked by fat accumulation and inflammation, partly due to impaired lipophagy—a cellular process in which lipid droplets are broken down through autophagy. Rubicon, a protein that inhibits this process, worsens the condition by blocking fat breakdown. Small interfering RNA molecules targeting Rubicon show therapeutic potential but face challenges such as instability and off-target effects. Here we show a dual-targeted nanoparticle system designed for efficient delivery of Rubicon-targeting small interfering RNA to liver cells. This system has a core-shell structure that ensures stability in the bloodstream and responsiveness to oxidative stress, commonly found in metabolic dysfunction-associated steatotic liver disease. Once inside the liver cells, the nanoparticles release the RNA molecules, which reduce Rubicon levels, restore lipophagy, and alleviate fatty liver buildup. This strategy offers a flexible platform for targeted gene silencing therapy in liver diseases. |
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| ISSN: | 2041-1723 |