Polyethylene Glycol-coated Gold Nanoparticles Research Articles

Assessing the toxicity of one-step-synthesized PEG-coated gold nanoparticles: in vitro and in vivo studies.

To evaluate the in vitro and in vivo toxicities of polyethylene glycol-coated gold nanoparticles synthesized using a one-step process. Gold nanoparticles were prepared via a co-precipitation method using polyethylene glycol, and the synthesis product was characterized. For the in vitro evaluation, a flow cytometry analysis with Annexin V and iodide propidium staining was used to assess cytotoxicity in MG-63 cells labeled with 10, 50, and 100µg/mL of nanoparticle concentration. For the in vivo evaluation, nanoparticles were administered intraperitoneally at a dose of 10mg/kg dose in 10-week-old mice. Toxicity was assessed 24 hours and 7 days after administration via histopathological analysis of various tissues, as well as through renal, hepatic, and hematopoietic evaluations. Synthesized nanoparticles exhibited different hydrodynamic sizes depending on the medium: 51.27±1.62nm in water and 268.12±28.45nm (0 hour) in culture medium. They demonstrated a maximum absorbance at 520nm and a zeta potential of -8.419mV. Cellular viability exceeded 90%, with less than 3% early apoptosis, 6% late apoptosis, and 1% necrosis across all labeling conditions, indicating minimal cytotoxicity differences. Histopathological analysis highlighted the accumulation of nanoparticles in the mesentery; however, no lesions or visible agglomeration was observed in the remaining tissues. Renal, hepatic, and hematopoietic analyses showed no significant differences at any time point. Polyethylene glycol-coated gold nanoparticles exhibit extremely low toxicity and high biocompatibility, showing promise for future studies.

Mammalian Cells Exocytose Alkylated Gold Nanoparticles via Extracellular Vesicles.

Understanding the exocytosis of nanoparticles (NPs) from cells is valuable because it informs design rules of NPs that support desirable cellular retention for nanomedicine applications, but investigations into the mechanism for the exocytosis of NPs remain scarce. We elucidate the mechanism for the exocytosis of dodecyl-terminated, polyethylene glycol-coated gold NPs (termed "dodecyl-PEG-AuNP"). The Au core enables ultrastructural differentiation of the exocytosed NPs from the nearby extracellular vesicles (EVs). The PEG shell prevents interparticle agglomeration or aggregation that disfavors exocytosis. The minute amounts of alkyl chains on the PEG shell not only promote cellular uptake but also improve exocytosis by up to 4-fold higher probability and upregulate exocytosis- and vesicle-related genes. After entering Kera-308 keratinocytes and trafficking to multivesicular bodies and lysosomes, these NPs exit the cell predominantly via unconventional exocytosis, accompanied by enhanced secretion of sub-100 nm, CD81-enriched exosomes. The pathway for NP exocytosis and subpopulation of EVs that are secreted alongside the exocytosed NPs depends on dodecyl loading. This work provides insights into dissecting the mechanism of NP exocytosis and its relationship with EV secretion.

Pharmacokinetics of PEGylated Gold Nanoparticles: In Vitro-In Vivo Correlation.

Data suitable for assembling a physiologically-based pharmacokinetic (PBPK) model for nanoparticles (NPs) remain relatively scarce. Therefore, there is a trend in extrapolating the results of in vitro and in silico studies to in vivo nanoparticle hazard and risk assessment. To evaluate the reliability of such approach, a pharmacokinetic study was performed using the same polyethylene glycol-coated gold nanoparticles (PEG-AuNPs) in vitro and in vivo. As in vitro models, human cell lines TH1, A549, Hep G2, and 16HBE were employed. The in vivo PEG-AuNP biodistribution was assessed in rats. The internalization and exclusion of PEG-AuNPs in vitro were modeled as first-order rate processes with the partition coefficient describing the equilibrium distribution. The pharmacokinetic parameters were obtained by fitting the model to the in vitro data and subsequently used for PBPK simulation in vivo. Notable differences were observed in the internalized amount of Au in individual cell lines compared to the corresponding tissues in vivo, with the highest found for renal TH1 cells and kidneys. The main reason for these discrepancies is the absence of natural barriers in the in vitro conditions. Therefore, caution should be exercised when extrapolating in vitro data to predict the in vivo NP burden and response to exposure.

A new strategy based on polyethylene glycol coated gold nanoparticles to enhance the sensitivity of radiotherapy for glioma

Radiotherapy (RT), as an essential method for glioma treatment, can effectively kill tumor cells. However, radiation resistance of blood–brain barrier and glioma cells leads to poor efficacy of RT, which cannot effectively improve the survival time of patients. Therefore, designing methods to improve the sensitivity of glioma cells to radiation is the key to improve the effect of RT. We propose a novel strategy for radiosensitizing glioma cells based on gold nanoparticles coated with polyethylene glycol. Results of clone formation experiments demonstrated that the Au NPs@PEG radiosensitization ratio (SER) was as high as 1.74, which effectively improved the killing effect of X-rays on the tumor. We successfully established a glioma mouse model and applied Au NPs@PEG to RT. Results of in vivo experiments showed that Au NPs@PEG combined with X-rays can significantly reduce the expression of tumor-related molecules and effectively inhibit the process of tumor invasion, proliferation, and migration.

Migration of polyethylene glycol coated gold nanoparticles in surrogate natural barriers

ABSTRACT Introduction Studies on migration behaviors of colloidal materials through engineered and natural barriers are highly important for the safety assessment of radioactive waste repositories since the fate and transport of radionuclides may be significantly affected by interactions with colloids.Methods: Poly (ethylene glycol) coated gold nanoparticles (AuNPs) were used as a model colloid and the effects of the properties of AuNPs on their migration behaviors were investigated in batch and column experiments with silica sand.Results: Deposition of AuNPs on silica sand and aggregation of AuNPs were observed more for larger AuNPs despite the unfavorable conditions of both AuNPs and silica sand having overall negative surface charges. Sloping plateaus were observed in the breakthrough curves, suggesting that a limited number of sites arising from charge heterogeneities on silica sand may be responsible for attractive forces between AuNPs and silica sand. However, stronger affinity toward silica sand and with each other was observed for larger AuNPs which have more significant negative surface charges.Conclusions: The results suggest that interactions other than electrostatic and van der Waals (vdW) are controlling the migration behavior of AuNPs, including steric effects arising from the surface coating, thus need to be considered when assessing fate and transport of nanoparticles.

Comparison of Gold Nanoparticles and Iodinated Contrast Media in Radiation Dose Reduction and Contrast Enhancement in Computed Tomography

Background: Gold nanoparticles with high atomic number and density have good potential to be used as contrast media in computed tomography. Objectives: In this study, we aimed to assess radiation dose and contrast enhancement performance of gold nanoparticles by measuring contrast to noise ratio compared to clinically used iodinated contrast agents at same concentrations. Contrast enhancement was evaluated in different tube voltages and currents. Materials and Methods: First, polyethylene glycol coated gold nanoparticles were synthesized with concentrations of 0.5 mM, 0.6 mM, and 0.7 mM. Gold nanoparticles and iodinated contrast media were scanned with CT imaging system at different tube voltages and time-current product. CT dose index (CTDI) value was measured by special phantom and electrometer. Improving in image contrast was assessed by contrast to noise ratio. Results: Results showed that gold nanoparticles in all concentrations and energies from 80 to 130 kVp display higher image contrast-to-noise ratio (CNR) than iodinated contrast media. Image CNR was increased by increasing kVp and mAs. The CNR value was maximum at the voltage of 80 and 130 kVp for iodinated compounds and gold nanoparticles, respectively. The CNR value for gold nanoparticles at 130 kVp and 200 mAs was approximately five times higher than that of iodinated compounds. Conclusion: Gold nanoparticles could be a good candidate for optimizing CT imaging by lowering radiation dose as low as possible while enhancing the image contrast.

Intrapulmonary Cellular-Level Distribution of Inhaled Nanoparticles with Defined Functional Groups and Its Correlations with Protein Corona and Inflammatory Response.

Concerns over the health risks associated with airborne exposure to ultrafine particles [PM0.1, or nanoparticles (NPs)] call for a comprehensive understanding in the interactions of inhaled NPs along their respiratory journey. We prepare a collection of polyethylene glycol-coated gold nanoparticles that bear defined functional groups commonly identified in atmospheric particulates (Au@PEG-X NPs, where X = OCH3, COOH, NH2, OH, or C12H25). Regardless of the functional group, these ∼50 nm NPs remain colloidally stable following aerosolization and incubation in bronchoalveolar lavage fluid (BALF), without pronouncedly crossing the air-blood barrier. The type of BALF proteins adhered onto the NPs is similar, but the composition of protein corona depends on functional group. By subjecting Balb/c mice to inhalation of Au@PEG-X NPs for 6 h, we demonstrate that the intrapulmonary distribution of NPs among the various types of cells (both found in BALF and isolated from the lavaged lung) and the acute inflammatory responses induced by inhalation are sensitive to the functional group of NPs and postinhalation period (0, 24, or 48 h). By evaluating the pairwise correlations between the three variables of "lung-nano" interactions (protein corona, intrapulmonary cellular-level distribution, and inflammatory response), we reveal strong statistical correlations between the (1) fractions of albumin or carbonyl reductase bound to NPs, (2) associations of inhaled NPs to neutrophils in BALF or macrophages in the lavaged lung, and (3) level of total protein in BALF. Our results provide insights into the effect of functional group on lung-nano interactions and health risks associated with inhalation of PM0.1.

Endocytosis mechanism in physiologically-based pharmacokinetic modeling of nanoparticles

BackgroundThe physiologically based pharmacokinetic (PBPK) model is a useful tool to predict the pharmacokinetics of various types of nanoparticles (NPs). The endocytosis mechanism plays a key role in pharmacokinetics of NPs. However, the effect of endocytosis mechanism both in the blood and tissue are seldom considered in PBPK model. ObjectivesTo investigate the biodistribution of intravenously injected pegylated AuNPs in mice and human using PBPK model considering the endocytosis mechanism both in the blood and tissue. MethodsTaking polyethylene glycol-coated gold nanoparticles (AuNPs) as an example, we developed a PBPK model to explore biodistribution of different size AuNPs. In the model, we considered the role of endocytosis mechanism both in the blood and tissue. In addition, the size-dependent permeability coefficient, excretion rate constant, phagocytic capacity, uptake rate, and release rate were derived from literatures. The mice PBPK model was extrapolated to the human by changing physiology parameters and the number of phagocytic cell (PCs). ResultsAuNPs were primarily distributed in the blood, liver, and spleen regardless of particle size, and almost all captured by the PCs in the liver and spleen, while few was captured in the blood. There are more organ distribution and longer circulation for smaller NPs. The 24-h accumulation of AuNPs decreased with increasing size in the most organ, while the accumulation of AuNPs showed an inverted U-shaped curve in the liver and slight U-shaped curve in the blood. The human results of model-predicted displayed a similar tendency with those in mice. Size, partition coefficients, and body weight were the key factors influencing the organ distribution of AuNPs. ConclusionsThe size played an important role on the distribution and accumulation of AuNPs in various tissues. Our PBPK model was well predicted the NPs distribution in mice and human. A better understanding of these mechanisms could provide effective guides for nanomedine delivery.

Polyethylene Glycol-Coated Gold Nanoparticles as DNA and Atorvastatin Delivery Systems and Cytotoxicity Evaluation

The application of nanoscience and nanotechnology in medicine has been useful in the diagnosis, monitoring, and treatment of many diseases. Gold nanoparticles are commonly used for medical imaging studies, biosensors, drug delivery systems, and gene therapy. It has been reported that nanoparticles coated with specific polymers improve the biocompatibility and stability and decrease the cytotoxicity of the nanoparticles. In this work, we performed transfection studies of gold nanoparticles coated with polyethylene glycol, synthetized by two different methods, in a human embryonic kidney cell culture (HEK 293), by using plasmids pSV-β-Gal and pIRES2-EGFP. In addition, we also evaluated the cell uptake of a fluorescent drug (atorvastatin) using the synthetized gold nanoparticles as carriers. Furthermore, the study of cell viability after the interaction between these cells and the nanoparticles was performed. It was shown that the polyethylene glycol-coated gold nanoparticles presented transfection efficiency and cell uptake greater than 45% in each case. These results suggest that the synthetized gold nanoparticles coated with polyethylene glycol could be used successfully and safely as DNA and drug delivery systems.

Gold Nanoparticle-Based Fluorescent Theranostics for Real-Time Image-Guided Assessment of DNA Damage and Repair.

Chemotherapeutic dosing, is largely based on the tolerance levels of toxicity today. Molecular imaging strategies can be leveraged to quantify DNA cytotoxicity and thereby serve as a theranostic tool to improve the efficacy of treatments. Methoxyamine-modified cyanine-7 (Cy7MX) is a molecular probe which binds to apurinic/apyrimidinic (AP)-sites, inhibiting DNA-repair mechanisms implicated by cytotoxic chemotherapies. Herein, we loaded (Cy7MX) onto polyethylene glycol-coated gold nanoparticles (AuNP) to selectively and stably deliver the molecular probe intravenously to tumors. We optimized the properties of Cy7MX-loaded AuNPs using optical spectroscopy and tested the delivery mechanism and binding affinity using the DLD1 colon cancer cell line in vitro. A 10:1 ratio of Cy7MX-AuNPs demonstrated a strong AP site-specific binding and the cumulative release profile demonstrated 97% release within 12 min from a polar to a nonpolar environment. We further demonstrated targeted delivery using imaging and biodistribution studies in vivo in an xenografted mouse model. This work lays a foundation for the development of real-time molecular imaging techniques that are poised to yield quantitative measures of the efficacy and temporal profile of cytotoxic chemotherapies.

The Effect of Gold Nanoparticle Surface Modification with Polyethylene Glycol on the Absorbed Dose Distribution upon Irradiation with 137Cs and 60Co Photons

Abstract—Modification of the surface of gold nanoparticles with polyethylene glycol (PEG) is widely used to investigate radiosensitization in vivo. This modification may lead to alterations in the spectral characteristics of secondary radiation emitted by gold nanoparticles under the influence of photons. Using a Monte-Carlo calculation, we found that upon irradiation of 17-nm gold nanoparticles coated with a 8.5-nm polyethylene glycol shell with 137Cs (Eav = 0.667 MeV) and 60Co (Eav = 1.25 MeV) photons, 53.9% (137Cs) and 51.3% (60Co) of ionization electrons (Auger, Coster–Kronig, and fluorescence), 7.1% (137Cs) and 0.9% (60Co) of the photoelectrons were absorbed, and 32.6% (137Cs) and 27.4% (60Co) of the Compton electrons; as well 0.4% (137Cs) and 9.7% (60Co) of the secondary photons were additionally generated in the polymer shell. The surface modification with polyethylene glycol led to shielding of the high-absorption dose area: the ratio of the absorbed doses for the unmodified and polyethylene glycol-coated gold nanoparticles differed by 1.3–9 times. Since the radiosensitizing efficacy of gold nanoparticles depends on the characteristics of the secondary radiation, the optimization of surface coatings is an important step in rational drug design.

Effect of Alkylation on the Cellular Uptake of Polyethylene Glycol-Coated Gold Nanoparticles.

Alkyl groups (CnH2n+1) are prevalent in engineered bionanomaterials used for many intracellular applications, yet how alkyl groups dictate the interactions between nanoparticles and mammalian cells remains incomprehensively investigated. In this work, we report the effect of alkylation on the cellular uptake of densely polyethylene glycol-coated nanoparticles, which are characterized by their limited entry into mammalian cells. Specifically, we prepare densely PEGylated gold nanoparticles that bear alkyl chains of varying carbon chain lengths (n) and loading densities (termed "alkyl-PEG-AuNPs"), followed by investigating their uptake by Kera-308 keratinocytes. Strikingly, provided a modest alkyl mass percentage of 0.2% (2 orders of magnitude lower than that of conventional lipid-based NPs) in their PEG shells, dodecyl-PEG-AuNPs (n = 12) and octadecyl-PEG-AuNPs (n = 18) can enter Kera-308 cells 30-fold more than methoxy-PEG-AuNPs (no alkyl groups) and hexyl-PEG-AuNPs (n = 6) after 24 h of incubation. Such strong dependence on n is valid for all serum concentrations considered (even under serum-free conditions), although enhanced serum levels can trigger the agglomeration of alkyl-PEG-AuNPs (without permanent aggregation of the AuNP cores) and can attenuate their cellular uptake. Additionally, alkyl-PEG-AuNPs can rapidly enter Kera-308 cells via the filipodia-mediated pathway, engaging the tips of membrane protrusions and accumulating within interdigital folds. Most alkyl-PEG-AuNPs adopt the "endo-lysosomal" route of trafficking, but ∼15% of them accumulate in the cytosol. Regardless of intracellular location, alkyl-PEG-AuNPs predominantly appear as individual entities after 24 h of incubation. Our work offers insights into the incorporation of alkyl groups for designing bionanomaterials for cellular uptake and cytosolic accumulation with intracellular stability.

Basic Physicochemical Properties of Polyethylene Glycol Coated Gold Nanoparticles that Determine Their Interaction with Cells

AbstractA homologous nanoparticle library was synthesized in which gold nanoparticles were coated with polyethylene glycol, whereby the diameter of the gold cores, as well as the thickness of the shell of polyethylene glycol, was varied. Basic physicochemical parameters of this two‐dimensional nanoparticle library, such as size, ζ‐potential, hydrophilicity, elasticity, and catalytic activity ,were determined. Cell uptake of selected nanoparticles with equal size yet varying thickness of the polymer shell and their effect on basic structural and functional cell parameters was determined. Data indicates that thinner, more hydrophilic coatings, combined with the partial functionalization with quaternary ammonium cations, result in a more efficient uptake, which relates to significant effects on structural and functional cell parameters.

Basic Physicochemical Properties of Polyethylene Glycol Coated Gold Nanoparticles that Determine Their Interaction with Cells.

A homologous nanoparticle library was synthesized in which gold nanoparticles were coated with polyethylene glycol, whereby the diameter of the gold cores, as well as the thickness of the shell of polyethylene glycol, was varied. Basic physicochemical parameters of this two-dimensional nanoparticle library, such as size, ζ-potential, hydrophilicity, elasticity, and catalytic activity ,were determined. Cell uptake of selected nanoparticles with equal size yet varying thickness of the polymer shell and their effect on basic structural and functional cell parameters was determined. Data indicates that thinner, more hydrophilic coatings, combined with the partial functionalization with quaternary ammonium cations, result in a more efficient uptake, which relates to significant effects on structural and functional cell parameters.

Intraspinal Delivery of Polyethylene Glycol-coated Gold Nanoparticles Promotes Functional Recovery After Spinal Cord Injury

Failure of the mammalian central nervous system (CNS) to regenerate effectively after injury leads to mostly irreversible functional impairment. Gold nanoparticles (AuNPs) are promising candidates for drug delivery in combination with tissue-compatible reagents, such as polyethylene glycol (PEG). PEG administration in CNS injury models has received interest for potential therapy, but toxicity and low bioavailability prevents clinical application. Here we show that intraspinal delivery of PEG-functionalized 40-nm-AuNPs at early stages after mouse spinal cord injury is beneficial for recovery. Positive outcome of hind limb motor function was accompanied by attenuated inflammatory response, enhanced motor neuron survival, and increased myelination of spared or regrown/sprouted axons. No adverse effects, such as body weight loss, ill health, or increased mortality were observed. We propose that PEG-AuNPs represent a favorable drug-delivery platform with therapeutic potential that could be further enhanced if PEG-AuNPs are used as carriers of regeneration-promoting molecules.

A physiologically based pharmacokinetic model for polyethylene glycol-coated gold nanoparticles of different sizes in adult mice

Nanoparticles (NPs) are widely used in various fields of nanomedicine. A systematic understanding of NP pharmacokinetics is crucial in their design, applications, and risk assessment. In order to integrate available experimental information and to gain insights into NP pharmacokinetics, a membrane-limited physiologically based pharmacokinetic (PBPK) model for polyethylene glycol-coated gold (Au) NPs (PEG-coated AuNPs) was developed in mice. The model described endocytosis of the NPs in the liver, spleen, kidneys, and lungs and was calibrated using data from mice that were intravenously injected with 0.85 mg/kg 13 nm and 100 nm PEG-coated AuNPs. The model adequately predicted multiple external datasets for PEG-coated AuNPs of similar sizes (13–20 nm; 80–100 nm), indicating reliable predictive capability in suitable size ranges. Simulation results suggest that endocytosis of NPs is time and size dependent, i.e. endocytosis of larger NPs occurs immediately and predominately from the blood, whereas smaller NPs can diffuse through the capillary wall and their endocytosis appears mainly from the tissue with a 10-h delay, which may be the primary mechanism responsible for the reported size-dependent pharmacokinetics of NPs. Several physiological parameters (e.g. liver weight fraction of body weight) were identified to have a high influence on selected key dose metrics, indicating the need for additional interspecies comparison and scaling studies and to conduct pharmacokinetic studies of NPs in species that are more closely related to humans in these parameters. This PBPK model provides useful insights into the size, time, and species dependence of NP pharmacokinetics.

Gold nanoparticles do not induce myotube cytotoxicity but increase the susceptibility to cell death

Gold nanoparticles (AuNP) have been widely used for many applications, including as biological carriers. A better understanding concerning AuNP safety on muscle cells is crucial, since it could be a potential tool in the nanomedicine field. Here, we describe the impact of polyethylene glycol-coated gold nanoparticles (PEG-AuNP) interaction with differentiated skeletal muscle C2C12 cells on cell viability, mitochondria function, cell signaling related to survival, cytokine levels and susceptibility to apoptosis. Intracellular localization of 4.5nm PEG-AuNP diameter size was evidenced by STEM-in-SEM in myotube cells. Methods for cytotoxicity analysis showed that PEG-AuNP did not affect cell viability, but intracellular ATP levels and mitochondrial membrane potential increased. Phosphorylation of ERK was not altered but p-AKT levels reduced (p<0.01). Pre-treatment of cells with PEG-AuNP followed by staurosporine induction increased the caspases-3/7 activity. Indeed, cytokines analysis revealed a sharp increase of IFN-γ and TGF-β1 levels after PEG-AuNP treatment, suggesting that inflammatory and fibrotic phenotypes process were activated. These data demonstrate that PEG-AuNP affect the myotube physiology leading these cells to be more susceptible to death stimuli in the presence of staurosporine. Altogether, these results present evidence that PEG-AuNP affect the susceptibility to apoptosis of muscle cells, contributing to development of safer strategies for intramuscular delivery.

Preparation of compact nanoparticle clusters from polyethylene glycol-coated gold nanoparticles by fine-tuning colloidal interactions.

Low-molecular weight polyethylene glycol (PEG) has a lower critical solution temperature well outside the boiling point of water at ambient pressure, but it can be reduced at high ionic strengths. We extend this concept to trigger the clustering of gold nanoparticles through the control of colloidal interactions. At high ionic strengths, low-molecular weight (<2000 Da) mPEG-SH-modified gold nanoparticles show clustering with an increase in the solution temperature. The clustering temperature decreases with an increasing ionic strength. The clustering is attributed to the delicate interplay between the high ionic strength and elevated temperature and is interpreted in terms of chain collapse of the surface-grafted PEG molecules. The chain collapse results in a change in the steric interaction term, whereas the high ionic strength eliminates the double-layer repulsion between the particles. The observations are backed by nanoparticle interaction model calculations. We found that the intermediate attractive potential on the order of a few kT allows the experimental fabrication of compact nanoparticle clusters in agreement with theoretical predictions. The approach presented here has the potential to be extended on the externally triggered preparation of nanoparticle clusters with different types of nanoparticles.

Structural characterization of functionalized gold nanoparticles for drug delivery in cancer therapy: a NMR based approach.

In the present paper, we report results from a study of the structure and physicochemical properties of gold nanoparticles modified with poly(ethylene glycol) (PEG) designed for the drug delivery of the proteasome inhibitor Bortezomib (BTZ) in cancer therapy. A number of advanced analytical techniques were used to define important physicochemical characteristics such as composition, structure, surface properties, particle size and morphology. A new approach based on detailed NMR studies was employed to define specific intermolecular interactions and mechanisms of drug immobilization and location into surface modified gold nanoparticles (AuNPs). Particularly important information was gained from analysis of NMR spectroscopic parameters such as the spectral line shape, translation diffusion, the nuclear Overhauser effect (NOE) and spin-lattice relaxation (T1). The results confirmed the coexistence of two different types of BTZ inclusion into polyethylene glycol coated gold nanoparticles: (i) association with the polymer chains by weak H-bonds and/or dipole-charge interactions and (ii) adsorption on the surface of the gold nanoparticles. The results allowed for determination of the overall structure of Bortezomib loaded PEG coated AuNPs, which is related to the therapeutic drug efficacy and activity in the treatment of cancer.

Organ-specific distribution of gold nanoparticles by their surface functionalization.

The behavior and fate of intravenously (i.v.) injected nanoparticles (NPs) can be controlled by several physicochemical factors including size, shape and surface charge. To evaluate the role of surface charge on distribution of NPs, we used neutral-charged 15-nm-sized polyethylene glycol-coated gold nanoparticles (AuNP(PEG)) as a core NP and carboxyl or amine groups were conjugated to AuNP(PEG) to generate negative (AuNP(COOH)) or positive AuNP (AuNP(NH2)), respectively. Each type of AuNP was i.v. injected into mice (1 mg kg(-1)) and the concentration of Au was measured in different organs at 30 min, 4, 24 h, 7, 14 days, 1, 3 and 6 months post-injection. The organ distribution also showed the higher deposition rate depending on their functional groups: AuNP(PEG) for mesenteric lymph node, kidney, brain and testis; AuNP(COOH) for liver; AuNP(NH2) for spleen, lung and heart. The blood circulation time and the major excretion route were different depending on their functional groups. In conclusion, functional groups conjugated on the surface of AuNPs produce differences in blood kinetics, organ distribution and elimination pattern which can be important information for directing NPs to specific organs or improving the kinetic properties.