title: Surface charge-mediated rapid hepatobiliary excretion of mesoporous silica nanoparticles.
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.
authors.affiliation: Department of Radiology, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Souris
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Lee
authors.forename: Shih-Hsun
authors.initials: SH
authors.lastname: Cheng
authors.forename: Chin-Tu
authors.initials: CT
authors.lastname: Chen
authors.forename: Chung-Shi
authors.initials: CS
authors.lastname: Yang
authors.forename: Ja-an A
authors.initials: JA
authors.lastname: Ho
authors.forename: Chung-Yuan
authors.initials: CY
authors.lastname: Mou
authors.forename: Leu-Wei
authors.initials: LW
authors.lastname: Lo
mesh_terms: D000818:Animals; D004396:Coloring Agents / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D007208:Indocyanine Green / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008422:Materials Testing; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry / Q000378:metabolism*; D013499:Surface Properties
chemical_list: D004396:Coloring Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D012822:Silicon Dioxide; D007208:Indocyanine Green