Abstract
BackgroundTo effectively applied nanomaterials (NMs) in medicine, one of the top priorities is to address a better understanding of the possible sub-organ transfer, clearance routes, and potential toxicity of the NMs in the liver and kidney.ResultsHere we explored how the surface chemistry of polyethylene glycol (PEG), chitosan (CS), and polyethylenimine (PEI) capped gold nanoparticles (GNPs) governs their sub-organ biodistribution, transfer, and clearance profiles in the liver and kidney after intravenous injection in mice. The PEG-GNPs maintained dispersion properties in vivo, facilitating passage through the liver sinusoidal endothelium and Disse space, and were captured by hepatocytes and eliminated via the hepatobiliary route. While, the agglomeration/aggregation of CS-GNPs and PEI-GNPs in hepatic Kupffer and endothelial cells led to their long-term accumulation, impeding their elimination. The gene microarray analysis shows that the accumulation of CS-GNPs and PEI-GNPs in the liver induced obvious down-regulation of Cyp4a or Cyp2b related genes, suggesting CS-GNP and PEI-GNP treatment impacted metabolic processes, while the PEI-GNP treatment is related with immune responses.ConclusionsThis study demonstrates that manipulation of nanoparticle surface chemistry can help NPs selectively access distinct cell types and elimination pathways, which help to clinical potential of non-biodegradable NPs.
Highlights
IntroductionTo effectively use NMs in biomedicine, the appropriate surface modifications are necessary in order for them to resist rapid clearance, pass-through biological barriers, and rapidly distribute to target organs and tissues [14]
To effectively applied nanomaterials (NMs) in medicine, one of the top priorities is to address a better understanding of the possible sub-organ transfer, clearance routes, and potential toxicity of the NMs in the liver and kidney
Dynamic light scattering measurements indicated that the hydrodynamic diameter of polyethylene glycol (PEG)-Gold nanoparticles (GNPs) in water was similar to Cit-GNPs, while much larger hydrodynamic diameters were obtained for CS-GNPs and PEI-GNPs in either water or saline solution, suggesting that the particles become agglomerated (Fig. 1b)
Summary
To effectively use NMs in biomedicine, the appropriate surface modifications are necessary in order for them to resist rapid clearance, pass-through biological barriers, and rapidly distribute to target organs and tissues [14]. GNPs can be modified to have surface functional groups containing thiols, phosphines, and amines that enhance their aqueous dispersibility, biocompatibility, and targeting efficacy, form gold nanoconjugates, and anchor additional moieties such as oligonucleotides, proteins, and antibodies for targeted effects [15, 16]. In drug-delivery and imaging applications, the hydrophilic moiety polyethylene glycol (PEG) is widely used as functional agent on the surface of GNPs to prolong blood circulation time after intravenous injection by reducing absorption of serum proteins and hindering uptake by macrophages [2, 17]. It is important to assess the diversity of NP functions; few studies have reported the effects of functional groups on in vivo hepatic and renal transfer and clearance of NPs
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