Carrier-Free Small Molecule-Assembled Nanoparticles for Treatment of Sepsis

Sepsis is a complex disorder with high morality. Overabundant inflammation can result in organ dysfunction, leading to a series of diseases. Drug delivery systems have improved drug efficacy and brought hope for sepsis treatment. However, the usage of various inorganic and organic carriers might increase the potential toxicity of nanoparticles (NPs) and make their clinical transformation more difficult. Rhubarb and epimedium show good anti-inflammation and metabolic disorder treatment potentials. A series of ingredients that can form nanoscale particles without any additives were found in rhubarb and epimedium decoction. Based on pharmacological activity and cost-effectiveness consideration, rhein and icariin were selected to self-assemble to construct NPs. The prepared NPs show good anti-inflammatory properties and alleviate ferroptosis in vitro and in vivo. Further research has found that the prepared rhein–icariin NPs (R–I NPs) mainly prolong the survival time of mice by maintaining the kidneys’ function in sepsis, which is consistent with the function of their formulation Compound rhubarb granule. The prepared carrier-free, safe, and traditional Chinese medicine (TCM)-derived NPs show great potential in drug delivery. This study also provides a safe and simple nanoplatform to treat sepsis, which may pave a way to design TCM-derived NPs for clinical translation.