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Targeted delivery and ROS-responsive release of celastrol by a macrophage membrane biomimetic liposome alleviates acute kidney injury
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DOI：10.1039/D6NR00641H.png)
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Abstract
En 中文
Acute kidney injury (AKI) is characterized by an abrupt decline in renal function; often resulting from dysregulated production of reactive oxygen species (ROS) and an excessive inflammatory response. Celastrol; known for its anti-inflammatory and antioxidant properties; emerges as a promising therapeutic candidate for AKI. However; its clinical application is impeded by poor aqueous solubility; limited renal accumulation; and potential tissue toxicity. In this study; we engineered a macrophage membrane-camouflaged; ROS-responsive liposomal nanoplatform encapsulating celastrol (MST) that integrates inflammation-directed targeting with microenvironment-triggered release. Experimental findings indicate that the preservation of macrophage membrane proteins allowed MST to selectively target inflamed renal tissues; where it was efficiently internalized by damaged renal tubular cells; enabling rapid local drug release in response to elevated ROS levels. MST markedly mitigated oxidative damage both in vitro and in vivo; inhibited renal cell apoptosis; and reduced the inflammatory response in a renal ischemia-reperfusion injury model. Ultimately; MST achieved superior improvements in renal function; outperforming both non-biomimetic and non-responsive comparators; while demonstrating a favorable preliminary systemic safety profile. This study introduces a promising ROS-responsive biomimetic platform for AKI intervention.
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