title: Biodistribution, excretion, and toxicity of mesoporous silica nanoparticles after oral administration depend on their shape.
abstract: Mesoporous silica nanoparticles (MSNs) have been proven to be effective drug carriers for oral delivery. However, little attention has been paid to their in vivo biodistribution and toxicity after oral administration. The effect of particle shape on their in vivo behavior is also unknown. In this study, we systematically studied the acute toxicity and biodistribution of three types of MSNs with aspect ratios (ARs) of 1, 1.75 and 5 after oral administration. The effect of particle shape as a key physicochemical parameter of MSNs was discussed. With the increase of AR, MSNs showed decreased in vivo biodegradation, systematic absorption and excretion, especially decreased liver distribution and urinal excretion. During the period of urinal excretion, MSNs induced a shape-dependent renal damage including hemorrhage, vascular congestion and renal tubular necrosis. These findings will enrich the knowledge to rationally engineer bionanomaterials, and bring new insights into nanotoxicity.
  
  
  BACKGROUND
  Advances in nanotechnology have resulted in improvement in drug delivery, of which mesoporous silica nanoparticles have been used as carriers for oral drugs. Nonetheless, studies on their absorption, distribution, metabolism, excretion (ADME) and toxicity still need to be performed. In this article, authors evaluated the effects of particle size and shape on in vivo behavior. The findings would shine light on future design of future drug delivery systems.
authors.affiliation: Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing P. R. China. Electronic address: linlinli@mail.ipc.ac.cn.
authors.forename: Linlin
authors.initials: L
authors.lastname: Li
authors.affiliation: Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing P. R. China.
authors.forename: Tianlong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing P. R. China.
authors.forename: Changhui
authors.initials: C
authors.lastname: Fu
authors.affiliation: Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing P. R. China.
authors.forename: Longfei
authors.initials: L
authors.lastname: Tan
authors.affiliation: Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing P. R. China.
authors.forename: Xianwei
authors.initials: X
authors.lastname: Meng
authors.affiliation: Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing P. R. China. Electronic address: liuhy@mail.ipc.ac.cn.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity* / Q000648:ultrastructure; D009336:Necrosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016062:Porosity; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity*; D014018:Tissue Distribution
chemical_list: D012822:Silicon Dioxide
keywords: Biodistribution; Mesoporous silica nanoparticles (MSNs); Oral administration; Shape; Toxicity