Surface charge-mediated rapid hepatobiliary excretion of mesoporous silica nanoparticles

  • Souris J
  • Lee C
  • Cheng S
 et al. 
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Abstract

Nanoparticle-assisted drug delivery has been emerging as an active research area in recent years. The in vivo biodistribution of nanoparticle and its following mechanisms of biodegradation and/or excretion determine the feasibility and applicability of such a nano-delivery platform in the practical clinical translation. In this work we report the synthesis of the highly positive charge, near-infrared fluorescent mesoporous silica nanoparticles (MSNs) that demonstrate rapid hepatobiliary excretion, for use as traceable drug delivery platforms of high capacity. MSNs were incorporated with near-infrared fluorescent dye indocyanine green (ICG) via covalent or ionic bonding, to derive comparable constructs of significantly different net surface charge. In vivo fluorescence imaging and subsequent inductively coupled plasma-mass spectroscopy of harvested tissues, urine, and feces revealed markedly different uptake and elimination behaviors between the two conjugations; with more highly charged moieties (+34.4 mV at pH 7.4) being quickly excreted from the liver into the gastrointestinal tract, while less charged moieties (-17.6 mV at pH 7.4) remained sequestered within the liver. Taken together, these findings suggest that charge-dependent adsorption of serum proteins greatly facilitates the hepatobiliary excretion of silica nanoparticles, and that nanoparticle residence time in vivo can be regulated by manipulation of surface charge. © 2010 Elsevier Ltd.

Author-supplied keywords

  • Drug delivery
  • Hepatobiliary excretion
  • In vivo clearance of nanoparticle
  • Mesoporous silica nanoparticle
  • Near-infrared fluorescence
  • Surface charge of nanoparticle

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Authors

  • Jeffrey S. Souris

  • Chia Hung Lee

  • Shih Hsun Cheng

  • Chin Tu Chen

  • Chung Shi Yang

  • Ja an A. Ho

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