Cargo-influences on the biodistribution of hollow mesoporous silica nanoparticles as studied by quantitative 19F-magnetic resonance imaging.

HYPOTHESIS Biodistribution is a key issue when it comes to medical applications of nanomaterials. Hollow mesoporous silica nanoparticles (HMSNs) loaded with fluorine compounds can be applied as positive magnetic resonance imaging (MRI) contrast agents (CAs). These CAs exhibit an unusual biodistribution which is influenced by the cargo and which could be linked to their serum protein adsorption behaviour. EXPERIMENTS HMSNs were post-synthetically loaded with perfluoro-15-crown-5-ether (PFCE). The 19F signal was quantified with MRI in a murine model. Furthermore protein adsorption tests were performed in full serum. FINDINGS Quantitative analysis of the 19F-signal revealed that the particles were exclusively accumulating in the liver 24h post-injection, and no accumulation in other reticuloendothelial system (RES) organs like spleen or lung was observed. The protein corona around non-loaded and loaded particles was therefore analysed, and more proteins adsorbed on PFCE-loaded particles as compared to the bare particles, and importantly, the amount of apolipoproteins A-1 and A-2, was clearly elevated for the PFCE-loaded particles. The results underline that the type of cargo may have major influences on the biodistribution of mesoporous silica drug vectors.

[1]  Liyi Shi,et al.  Biodistribution and toxicity of intravenously administered silica nanoparticles in mice , 2010, Archives of Toxicology.

[2]  K. Kikuchi,et al.  Multifunctional core–shell silica nanoparticles for highly sensitive (19)F magnetic resonance imaging. , 2014, Angewandte Chemie.

[3]  B. Hargreaves,et al.  Simultaneous T1 and B1+ Mapping Using Reference Region Variable Flip Angle Imaging , 2013, Magnetic resonance in medicine.

[4]  Cecilia Sahlgren,et al.  Mesoporous silica nanoparticles in medicine--recent advances. , 2013, Advanced drug delivery reviews.

[5]  Zongxi Li,et al.  Mesoporous silica nanoparticles in biomedical applications. , 2012, Chemical Society reviews.

[6]  Ying Wang,et al.  Mesoporous silica nanoparticles in drug delivery and biomedical applications. , 2015, Nanomedicine : nanotechnology, biology, and medicine.

[7]  C. Kranz,et al.  Intermediate pickering emulsion formation as a means for synthesizing hollow mesoporous silica nanoparticles , 2016 .

[8]  R. Müller,et al.  Influence of surface charge density on protein adsorption on polymeric nanoparticles: analysis by two-dimensional electrophoresis. , 2002, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[9]  A. von Eckardstein,et al.  High density lipoproteins and arteriosclerosis. Role of cholesterol efflux and reverse cholesterol transport. , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[10]  Jun Yang,et al.  High yield expression and purification of recombinant human apolipoprotein A-II in Escherichia coli , 2012, Journal of Lipid Research.

[11]  G. Cheon,et al.  Systemic and specific delivery of small interfering RNAs to the liver mediated by apolipoprotein A-I. , 2007, Molecular therapy : the journal of the American Society of Gene Therapy.

[12]  Patrick J. Gaffney,et al.  Quantitative “magnetic resonance immunohistochemistry” with ligand‐targeted 19F nanoparticles , 2004 .

[13]  Xinglu Huang,et al.  Single and repeated dose toxicity of mesoporous hollow silica nanoparticles in intravenously exposed mice. , 2011, Biomaterials.

[14]  Rolf Schubert,et al.  Probing different perfluorocarbons for in vivo inflammation imaging by 19F MRI: image reconstruction, biological half‐lives and sensitivity , 2014, NMR in biomedicine.

[15]  Stefan Tenzer,et al.  Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. , 2013, Nature nanotechnology.

[16]  Samuel A Wickline,et al.  Quantitative magnetic resonance fluorine imaging: today and tomorrow. , 2010, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[17]  M. Wahlgren,et al.  Protein adsorption to solid surfaces. , 1991, Trends in biotechnology.

[18]  M. Krafft,et al.  Fluorocarbons and fluorinated amphiphiles in drug delivery and biomedical research. , 2001, Advanced drug delivery reviews.

[19]  Bin Lou,et al.  High-density lipoprotein as a potential carrier for delivery of a lipophilic antitumoral drug into hepatoma cells. , 2005, World journal of gastroenterology.

[20]  K. Yano,et al.  Anomalous Pore Expansion of Highly Monodispersed Mesoporous Silica Spheres and Its Application to the Synthesis of Porous Ferromagnetic Composite , 2008 .

[21]  Arend Heerschap,et al.  Customizable, multi-functional fluorocarbon nanoparticles for quantitative in vivo imaging using 19F MRI and optical imaging. , 2010, Biomaterials.

[22]  Dong Chen,et al.  The shape effect of mesoporous silica nanoparticles on biodistribution, clearance, and biocompatibility in vivo. , 2011, ACS nano.

[23]  Kemin Wang,et al.  In vivo study of biodistribution and urinary excretion of surface-modified silica nanoparticles. , 2008, Analytical chemistry.

[24]  K. Kikuchi,et al.  Mesoporous silica nanoparticles for 19F magnetic resonance imaging, fluorescence imaging, and drug delivery† †Electronic supplementary information (ESI) available: Detailed synthetic procedure, experimental procedure and Fig. S1–S7. See DOI: 10.1039/c4sc03549f Click here for additional data file. , 2014, Chemical science.

[25]  Larissa Miller,et al.  Synthesis, characterization, and biodistribution of multiple 89Zr-labeled pore-expanded mesoporous silica nanoparticles for PET. , 2014, Nanoscale.

[26]  Yaping Li,et al.  In vivo biodistribution and urinary excretion of mesoporous silica nanoparticles: effects of particle size and PEGylation. , 2011, Small.

[27]  P. Vierling,et al.  Extended in vivo blood circulation time of fluorinated liposomes , 1993, FEBS letters.

[28]  Hamidreza Ghandehari,et al.  In vivo biodistribution and pharmacokinetics of silica nanoparticles as a function of geometry, porosity and surface characteristics. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[29]  S. Retterer,et al.  Dynamic development of the protein corona on silica nanoparticles: composition and role in toxicity. , 2013, Nanoscale.

[30]  Parag Aggarwal,et al.  Nanoparticle interaction with plasma proteins as it relates to particle biodistribution, biocompatibility and therapeutic efficacy. , 2009, Advanced drug delivery reviews.