Surface charge-mediated rapid hepatobiliary excretion of mesoporous silica nanoparticles

Jeffrey S. Souris, Chia Hung Lee, Shih Hsun Cheng, Chin Tu Chen, Chung Shi Yang, Ja an A. Ho, Chung Yuan Mou, Leu Wei Lo

Research output: Contribution to journalArticlepeer-review

244 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5564-5574
Number of pages11
JournalBiomaterials
Volume31
Issue number21
DOIs
Publication statusPublished - Jul 2010
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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