Biosafety of mesoporous silica nanoparticles: a combined experimental and literature study.

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.