Health and Medical Research Institute, Department of Life Science and Biotechnology, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan.
J Mater Sci Mater Med. 2021 Aug 18;32(9):102. doi: 10.1007/s10856-021-06582-y.
Mesoporous silica (MS) particles have been explored for various healthcare applications, but universal data about their safety and/or toxicity are yet to be well-established for clinical purposes. Information about general toxicity of hollow MS (HMS) particles and about immunotoxicity of MS particles are significantly lacked. Therefore, acute toxicity and immunotoxicity of HMS particles were experimentally evaluated. A systematic and objective literature study was parallelly performed to analyze the published in vivo toxicity of MS particles. Lethal acute toxicity of MS particles is likely to arise from their physical action after intravenous and intraperitoneal administrations, and only rarely observed after subcutaneous administration. No clear relationship was identified between physicochemical properties of MS particles and lethality as well as maximum tolerated dose with some exceptions. At sub-lethal doses, MS particles tend to accumulate mainly in lung, liver, and spleen. The HMS particles showed lower inflammation-inducing ability than polyinosinic-polycytidylic acid and almost the same allergy-inducing ability as Alum. Finally, the universal lowest observed adverse effect levels were determined as 0.45, 0.81, and 4.1 mg/kg (human equivalent dose) for intravenous, intraperitoneal, and subcutaneous administration of MS particles, respectively. These results could be helpful for determining an appropriate MS particle dose in clinical study.
介孔硅（MS）颗粒已被探索用于各种医疗保健应用，但就其安全性和/或毒性而言，尚无普遍适用于临床目的的确切数据。关于中空 MS（HMS）颗粒的一般毒性和 MS 颗粒的免疫毒性的信息非常缺乏。因此，我们对 HMS 颗粒的急性毒性和免疫毒性进行了实验评估。同时还平行进行了系统和客观的文献研究，以分析已发表的 MS 颗粒的体内毒性。MS 颗粒的静脉内和腹腔内给药后，其物理作用可能导致致命的急性毒性，而仅在皮下给药后很少观察到。除了一些例外情况，MS 颗粒的物理化学性质与致死率以及最大耐受剂量之间没有明显的关系。在亚致死剂量下，MS 颗粒倾向于主要在肺、肝和脾中积累。与聚肌苷酸-聚胞苷酸相比，HMS 颗粒的炎症诱导能力较低，与 Alum 几乎具有相同的过敏诱导能力。最后，确定静脉内、腹腔内和皮下给药的 MS 颗粒的通用最低观察到的不良反应水平分别为 0.45、0.81 和 4.1mg/kg（人体等效剂量）。这些结果有助于确定临床研究中 MS 颗粒的适当剂量。
