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Squalene-based multidrug nanoparticles for improved mitigation of uncontrolled inflammation in rodents #MMPMID32548259
Dormont F; Brusini R; Cailleau C; Reynaud F; Peramo A; Gendron A; Mougin J; Gaudin F; Varna M; Couvreur P
Sci Adv 2020[Jun]; 6 (23): eaaz5466 PMID32548259show ga
Uncontrolled inflammatory processes are at the root of numerous pathologies. Most recently, studies on confirmed COVID-19 cases have suggested that mortality might be due to virally induced hyperinflammation. Uncontrolled pro-inflammatory states are often driven by continuous positive feedback loops between pro-inflammatory signaling and oxidative stress, which cannot be resolved in a targeted manner. Here, we report on the development of multidrug nanoparticles for the mitigation of uncontrolled inflammation. The nanoparticles are made by conjugating squalene, a natural lipid, to adenosine, an endogenous immunomodulator, and then encapsulating alpha-tocopherol, as antioxidant. This resulted in high drug loading, biocompatible, multidrug nanoparticles. By exploiting the endothelial dysfunction at sites of acute inflammation, these multidrug nanoparticles delivered the therapeutic agents in a targeted manner, conferring survival advantage to treated animals in models of endotoxemia. Selectively delivering adenosine and antioxidants together could serve as a novel therapeutic approach for safe treatment of acute paradoxal inflammation.
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Sci+Adv 2020 ; 6 (23): eaaz5466
