Recently, mesoporous nanomaterials with widespread applications have attracted great interest in the field of drug delivery due to their unique structure and good physiochemical properties. As a biomimetic nanomaterial, mesoporous polydopamine (MPDA) possesses both a superior nature and good compatibility, endowing it with good clinical transformation prospects compared with other inorganic mesoporous nanocarriers. However, the subacute toxicity and underlying mechanisms of biomimetic mesoporous polydopamine nanoparticles remain uncertain. Herein, we prepared MPDAs by a soft template method and evaluated their primary physiochemical properties and metabolite toxicity, as well as potential mechanisms. The results demonstrated that MPDA injection at low (3.61 mg/kg) and medium doses (10.87 mg/kg) did not significantly change the body weight, organ index or routine blood parameters. In contrast, high-dose MPDA injection (78.57 mg/kg) is associated with disturbances in the gut microbiota, activation of inflammatory pathways through the abnormal metabolism of bile acids and unsaturated fatty acids, and potential oxidative stress injury. In sum, the MPDA dose applied should be controlled during the treatment. This study first provides a systematic evaluation of metabolite toxicity and related mechanisms for MPDA-based nanoparticles, filling the gap between their research and clinical transformation as a drug delivery nanoplatform.

中文翻译：

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仿生介孔聚多巴胺纳米粒子的亚急性毒性及其机制

近年来，具有广泛应用的介孔纳米材料因其独特的结构和良好的理化性质在药物递送领域引起了极大的兴趣。介孔聚多巴胺（MPDA）作为一种仿生纳米材料，兼具优越的性质和良好的相容性，与其他无机介孔纳米载体相比，具有良好的临床转化前景。然而，仿生介孔聚多巴胺纳米粒子的亚急性毒性和潜在机制仍不确定。在此，我们通过软模板法制备了MPDA，并评估了其主要理化性质和代谢物毒性以及潜在机制。结果表明，低剂量（3.61 mg/kg）和中剂量（10.87 mg/kg）注射MPDA并未显着改变体重、器官指数或血常规参数。相比之下，高剂量 MPDA 注射（78.57 mg/kg）与肠道微生物群紊乱、胆汁酸和不饱和脂肪酸异常代谢激活炎症途径以及潜在的氧化应激损伤有关。总之，治疗过程中应控制MPDA的剂量。这项研究首先对基于 MPDA 的纳米颗粒的代谢毒性和相关机制进行了系统评估，填补了其研究和作为药物输送纳米平台的临床转化之间的空白。