Biodistribution of colloidal gold nanoparticles after intravenous administration: effect of particle size.

Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, Japan.
Colloids and surfaces B: Biointerfaces (Impact Factor: 3.55). 11/2008; 66(2):274-80. DOI: 10.1016/j.colsurfb.2008.07.004
Source: PubMed

ABSTRACT Purpose of the present research work was to evaluate the biological distribution of differently size gold nanoparticles (NP) up on intravenous administration in mice. Another objective was to study effect of particle size on biological distribution of gold NP to enable their diverse applications in nanotechnology. Gold NP of different particle sizes, mainly 15, 50, 100 and 200 nm, were synthesized by modifying citrate ion concentration. Synthesized gold nanoparticles were characterized by SEM and their size distribution was studied by particle size analyzer. Gold NP was suspended in sodium alginate solution (0.5%, w/v) and administered to mice (1g/kg, intravenously) [n=3]. After 24h of administration of gold NP, blood was collected under light ether anesthesia, mice were sacrificed by cervical dislocation and various tissues/organs were removed. The tissues were then washed with saline, homogenized and lysed with aqua regia. The determination of gold in samples was carried out quantitatively by inductively coupled plasma mass spectrometry (ICP-MS). SEM study revealed spherical morphology of gold NP with narrow particle size distribution. Biodistribution study revealed gold NPs of all sizes were mainly accumulated in organs like liver, lung and spleen. The accumulation of gold NP in various tissues was found to be depending on particle size. 15 nm gold NP revealed higher amount of gold and number of particles in all the tissues including blood, liver, lung, spleen, kidney, brain, heart, stomach. Interestingly, 15 and 50 nm gold NP were able to pass blood-brain barrier as evident from gold concentration in brain. Two-hundred nanometers gold NP showed very minute presence in organs including blood, brain, stomach and pancreas. The results revealed that tissue distribution of gold nanoparticles is size-dependent with the smallest 15 nm nanoparticles showing the most widespread organ distribution.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The increasing use of nanomaterials raises concerns about the long-term effects of chronic nanoparticle exposure on human health. However, nanoparticle exposure is difficult to evaluate non-invasively using current measurement techniques. Here we show that the skin is an important site of nanoparticle accumulation following systemic administration. Mice injected with high doses of gold nanoparticles have visibly blue skin while quantum dottreated animals fluoresce under ultraviolet excitation. More importantly, elemental analysis of excised skin correlates with the injected dose and nanoparticle accumulation in the liver and spleen. We propose that skin analysis may be a simple strategy to quantify systemic nanoparticle exposure and predict nanoparticle fate in vivo. Our results suggest that in the future, dermal accumulation may also be exploited to trigger the release of ultraviolet and visible light-sensitive therapeutics that are currently impractical in vivo due to limits in optical penetration of tissues at these wavelengths.
    Nature Communications 05/2014; 5(3796). · 10.02 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Understanding the principles governing the design of nanoparticles for tumor targeting is essential for the effective diagnosis and treatment of solid tumors. There is currently a poor understanding of how to rationally engineer nanoparticles for tumor targeting. Here, we engineered different-sized spherical gold nanoparticles to discern the effect of particle diameter on passive (polyethylene glycol-coated) and active (transferrin-coated) targeting of MDA-MB-435 orthotopic tumor xenografts. Tumor accumulation of actively targeted nanoparticles was found to be five times faster and approximately two-fold higher relative to their passive counterparts within the 60 nm diameter range. We hypothesize that such enhancements are resultant of an increased capacity to penetrate into tumors and preferentially associate with cancer cells. We also use computational modelling to explore the mechanistic parameters that can impact tumor accumulation efficacy. We demonstrate that tumor accumulation can be mediated by high nanoparticle avidity and are weakly dependent on their plasma clearance rate. Such findings suggest that empirical models can be used to rapidly screen novel nanomaterials for relative differences in tumor targeting without the need for animal work. Although our findings are specific to MDA-MB-435 tumor xenografts, our experimental and computational findings help to enrich knowledge of design considerations that will aid in the optimal engineering of spherical gold nanoparticles for cancer applications in the future.
    ACS Nano 05/2014; · 12.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The endogenous deposition of protein fibrillar aggregates in the tissues is the cause of several neurodisorders. In the present study the native β-lactoglobulin (β-lg) has been driven towards amyloid fibrillar aggregates when it was exposed to heat at 75(0)C for 1h at pH 7.5. The citrate stabilized gold nanoparticle (AuNPs) of 20nm diameter is shown to inhibit the thermal aggregation of β-lg. The stability of the β-lg against heat stress was assessed by studying its aggregation at 75 (∘)C, either in presence or in absence of AuNPs. AuNPs stabilizes the monomeric and dimeric forms of the β-lg inhibiting the nucleation and elongation for the formation of higher aggregates. Incubation of β-lg with AuNPs at 75(0)C results in the formation of smaller ragged aggregates. Results show that AuNPs possess the capability of inhibiting the formation of amyloid fibrillar aggregates of β-lg in a concentration-dependent manner and may thus facilitate the refolding into native like structure. AuNPs thus serve as nano-chaperon to inhibit the protein aggregation. Thus chaperon like activity of AuNP may be exploited in the design of rational therapeutics for the neurodegenerative diseases.
    International journal of biological macromolecules 05/2014; · 2.37 Impact Factor

Full-text (2 Sources)

Available from
May 15, 2014