Biocompatible Gold Nanoparticles Research Articles

Current state and prospects of the phytosynthesized colloidal gold nanoparticles and their applications in cancer theranostics.

The design, development, and biomedical applications of phytochemical-based green synthesis of biocompatible colloidal gold nanoparticles (AuNPs) are becoming an emerging field due to several advantages (safer, eco-friendly, simple, fast, energy efficient, low-cost, and less toxic) over conventional chemical synthetic procedures. Biosynthesized colloidal gold nanoparticles are remarkably attractive in several biomedical applications including cancer theranostics due to small size, unusual physico-chemical properties, facile surface modification, high biocompatibility, and numerous other advantages. Of late, several researchers have investigated the biosynthesis and prospective applications (diagnostics, imaging, drug delivery, and cancer therapeutics) of AuNPs in health care and medicine. However, not a single review article is available in the literature that demonstrates the anti-cancer potential of biosynthesized colloidal AuNPs with detailed mechanistic study. In the present review article, we for the first time discuss the biointerface of colloidal AuNPs, plants, and cancer mainly (i) comprehensive mechanistic aspects of phytochemical-based synthesis of AuNPs; (ii) proposed anti-cancer mechanisms along with biomedical applications in diagnostics, imaging, and drug delivery; and (iii) key challenges for biogenic AuNPs as future cancer nanomedicine.

Pharmacological importance, characterization and applications of gold and silver nanoparticles synthesized by Panax ginseng fresh leaves

Previously, we showed the rapid and eco-friendly synthesis of gold and silver nanoparticles within 3 and 45 min by fresh leaves extract of herbal medicinal plant Panax ginseng. In addition, we characterized the nanoparticles in terms of shape, size, morphology and stability by FE-TEM, EDX, elemental mapping, SEAD, XRD and particles size analysis. In addition of this, we showed their antimicrobial, anti-coagulant, and biofilm inhibition activity of nanoparticles. Continuing our previous study, here we highlight the further characterization and biomedical applications of P. ginseng leaf-mediated gold and silver nanoparticles. We characterized the nanoparticles further in terms of active functional group and capping layer, surface charge, and temperature stability. Based on these factors, we explored the nanoparticles for antioxidant efficacy, biocompatibility in HaCaT cells, 3T3-L1 pre-adipocytes cells, for anticancer efficacy in A549 lung cancer and B16BL6 skin melenoma cancer cell lines and for anti-inflammation efficacy in RAW 264.7 cell lines. Based on our findings, we suggest that the P. ginseng-mediated gold nanoparticles have high antioxidant activity and highly biocompatibility in HaCaT cells, 3T3-L1 pre-adipocytes cells, RAW 264.7 cells lines and could be considered for future drug delivery carriers. The silver nanoparticles also showed high potent antioxidant efficacy, additionally it showed high anticancer effect in A549 lung cancer and B16BL6 skin melenoma cancer cell lines as compared to precursor salts. Moreover, both gold and silver nanoparticles have anti-inflammatory efficacies in RAW 264.7 cells. Thus, the study may provide useful insights of P. ginseng leaves extract-mediated biocompatible gold and silver nanoparticles and improving their applicability in designing nanoparticles carrier systems for drug delivery applications.

Flower-shaped gold nanoparticles synthesized using Kedrostis foetidissima and their antiproliferative activity against bone cancer cell lines

Three different methods were employed for the synthesis of biogenic gold nanoparticles using the aqueous extracts of Kedrostis foetidissima. The interaction of gold nanoparticles with the phytoconstituents was investigated by FTIR. The complete reduction of chloroaurate ions to gold nanoparticles was monitored using UV–visible spectroscopy under the different plant extract concentration and conditions. The formation of gold nanoparticles was confirmed using XRD, SEM and TEM analysis. The anisotropic and flower-shaped gold nanoparticles of size below 25 nm was confirmed by TEM analysis. Cucurbitacins, the chief constituents of K. foetidissima probably might have interacted with the chloroaurate ions, facilitating the formation of gold nanoparticles. KFL-mediated AuNPs showed 88 % cell viability against bone cancer cell lines at 200 µg/ml concentration using MTT assay. This may be due to the formation of flower-shaped nature of KFL-mediated AuNPs. The novelty of the work lies in the plant-mediated synthesis of biocompatible gold nanoparticles of size less than 25 nm showing 88 % of cell viability against bone cancer cell lines.

Photochemically-assisted synthesis of non-toxic and biocompatible gold nanoparticles

This contribution describes the photochemically-assisted synthesis of aqueous colloidal suspensions of non-toxic and biocompatible spherical gold nanoparticles stabilized by branched polyethylenimine, or else Au-np-PEI. The method consists on 30min of photoexcitation (254nm, 16W) at room temperature of an aqueous diluted solution of chloroauric acid (HAuCl4) containing PEI. While the UV irradiation forms the [Au(3+)Cl4−]* excited species that succesively transforms into zero valent Au, PEI controls the nucleation step of nanoparticles formation. Varying the PEI to Au molar ratio permits one to tune the size of nanoparticles between 100nm to 8nm. The obtained colloidal suspensions display an intense plasmonic absorption band at 520–530nm and positive zeta potentials greater than +20mV. The cells viability for in vitro tests performed with human connective tissues and human breast adenocarcinoma (MCF-7) cell lines is over 80% and 90%, respectively, when they are incubated with Au-np-PEI formulations (25μgmL−1). The present photochemically-assisted synthesis is advantageous because it is fast and does not require for either hazardous or cytotoxic reductant agents and additional purification procedures.

Guidable Thermophoretic Janus Micromotors Containing Gold Nanocolorifiers for Infrared Laser Assisted Tissue Welding.

Current wound sealing systems such as nanoparticle‐based gluing of tissues allow almost immediate wound sealing. The assistance of a laser beam allows the wound sealing with higher controllability due to the collagen fiber melting which is defined by loss of tertiary protein structure and restoration upon cooling. Usually one employs dyes to paint onto the wound, if water absorption bands are absent. In case of strong bleeding or internal wounds such applications are not feasible due to low welding depth in case of water absorption bands, dyes washing off, or the dyes becoming diluted within the wound. One possible solution of these drawbacks is to use autonomously movable particles composing of biocompatible gold and magnetite nanoparticles and biocompatible polyelectrolyte complexes. In this paper a proof of principle study is presented on the utilization of thermophoretic Janus particles and capsules employed as dyes for infrared laser‐assisted tissue welding. This approach proves to be efficient in sealing the wound on the mouse in vivo. The temperature measurement of single particle level proves successful photothermal heating, while the mechanical characterizations of welded liver, skin, and meat confirm mechanical restoration of the welded biological samples.

Paclitaxel-loaded chitosan oligosaccharide-stabilized gold nanoparticles as novel agents for drug delivery and photoacoustic imaging of cancer cells

Polymer nanoparticles have gained significant attention as potential drug carriers for anticancer agents and molecular imaging. Biocompatible gold nanoparticles (AuNPs) were synthesized using chitosan oligosaccharide (COS) as a reducing and stabilizing agent and were subsequently loaded with paclitaxel (PTX) to demonstrate their use in drug delivery and photoacoustic imaging (PAI) of MDA-MB-231 cells. Paclitaxel-loaded chitosan oligosaccharide-stabilized gold nanoparticles (PTX-COS AuNPs) were spherical in shape with an average particle size of 61.86±3.01nm. PTX-COS AuNPs showed sustained and pH-dependent drug release profiles and exhibited strong cytotoxic effect against MDA-MB-231 cells through the induction of apoptosis with improved reactive oxygen species (ROS) generation and altered mitochondrial membrane potential (MMP) level. The cellular internalization of PTX-COS AuNPs was proven by fluorescence microscopy as well as flow cytometry. PTX-COS AuNPs were also evaluated as a new class of optical contrast agents for photoacoustic imaging (PAI). To the best of our knowledge, this is the first report that describes the use of PTX-COS AuNPs as novel agents for drug delivery and PAI of cancer cells. These results exposed the promising potential of PTX-COS AuNPs in the field of drug delivery, molecular imaging, and cancer therapy in the near future.

Selective killing of cancer cells by nanoparticle-assisted ultrasound.

BackgroundIntense ultrasound, such as that used for tumor ablation, does not differentiate between cancerous and normal cells. A method combining ultrasound and biocompatible gold or magnetic nanoparticles (NPs) was developed under in vitro conditions using human breast and lung epithelial cells, which causes ultrasound to preferentially destroy cancerous cells.ResultsCo-cultures of BEAS-2B normal lung cells and A549 cancerous lung cells labeled with green and red fluorescent proteins, respectively, were treated with focused ultrasound beams with the addition of gold and magnetic nanoparticles. There were significantly more necrotic A549 cells than BEAS-2 cells when gold nanoparticles were added to the culture medium [(50.6 ± 15.1) vs. (7.4 ± 2.9) %, respectively, P < 0.01]. This selective damage to cancer cells was also observed for MDA-MB231 breast cancer cells relative to MCF-10A normal breast cells after treatment with magnetic nanoparticles.ConclusionsThe data obtained for different cell lines indicate that nanoparticle-assisted ultrasound therapy (NAUT) could be an effective new tool for cancer-specific treatment and could potentially be combined with conventional methods of cancer diagnosis and therapy to further increase the overall cancer cure rate.

Bioinorganic Interface: Mechanistic Studies of Protein-Directed Nanomaterial Synthesis

Proteins and peptides have attracted much attention as templates for one-pot synthesis of biocompatible gold nanoparticles. While numerous natural and de novo protein sequences have been used, the actual mechanism of nanoparticle nucleation and growth from the protein matrix is not well understood. In this study we utilized engineered consensus tetratricopeptide repeat protein (CTPR) to probe the bioinorganic interface during gold nanoparticle synthesis. The binding of CTPR to gold ions and the gold nanoparticle surface was investigated using fluorescence spectroscopy and heteronuclear single quantum coherence NMR spectroscopy to provide residue-specific measurements. This work provides a foundation for the rational design of proteins for synthesis of tailored functional nanomaterials for biological, medical, and optical applications.

Biomimetic synthesis of highly biocompatible gold nanoparticles with amino acid-dithiocarbamate as a precursor for SERS imaging

Amino acid-dithiocarbamate (amino acid-DTC) was developed as both the reductant and ligand stabilizer for biomimetic synthesis of gold nanoparticles (AuNPs), which served as an excellent surface-enhanced Raman scattering (SERS) contrast nanoprobe for cell imaging. Glycine (Gly), glutamic acid (Glu), and histidine (His) with different isoelectric points were chosen as representative amino acid candidates to synthesize corresponding amino acid-DTC compounds through mixing with carbon disulfide (CS2), respectively. The pyrogenic decomposition of amino acid-DTC initiated the reduction synthesis of AuNPs, and the strong coordinating dithiocarbamate group of amino acid-DTC served as a stabilizer that grafted onto the surface of the AuNPs, which rendered the as-prepared nanoparticles a negative surface charge and high colloidal stability. MTT cell viability assay demonstrated that the biomimetic AuNPs possessed neglectful toxicity to the human hepatoma cell, which guaranteed them good biocompatibility for biomedical application. Meanwhile, the biomimetic AuNPs showed a strong SERS effect with an enhancement factor of 9.8 × 105 for the sensing of Rhodamine 6G, and two distinct Raman peaks located at 1363 and 1509 cm−1 could be clearly observed in the cell-imaging experiments. Therefore, biomimetic AuNPs can be explored as an excellent SERS contrast nanoprobe for biomedical imaging, and the amino acid-DTC mediated synthesis of the AuNPs has a great potential in bio-engineering and biomedical imaging applications.

Polymeric nanoparticle systems for non-viral gene delivery

Event Abstract Back to Event Polymeric nanoparticle systems for non-viral gene delivery Corey J. Bishop1*, Stephany Y. Tzeng1*, Kristen L. Kozielski1*, Alfredo Quinones-Hinojosa2, 3* and Jordan Green1, 2, 3 1 Johns Hopkins University School of Medicine, Biomedical Engineering, United States 2 Johns Hopkins University School of Medicine, Neurosurgery, United States 3 Johns Hopkins University School of Medicine, Oncology, United States Introduction: Through engineering polymer and nanoparticle properties, non-viral intracellular delivery of DNA and siRNA can be made efficacious. By delivering DNA in conjunction with inorganic nanoparticles, such as biocompatible gold nanoparticles, therapeutic function (gene/thermotherapy) can be combined with diagnostic function (imaging). Figure 1. Representative PBAE polymer 447 Materials and Methods: Libraries of poly(beta-amino esters) (PBAEs) were synthesized as described[1]. As an example, to synthesize polymer 447 (Figure 1), 1,4-butanediol diacrylate and 4-amino-1-butanol were reacted neat in a 1.2:1 molar ratio for 24 hrs. Subsequently, the linear polymers were end-capped with 1-(3-aminopropyl)-4-methylpiperazine in anhydrous tetrahydrofuran (THF) for 1 hour at 1000 RPM. Polymeric nanoparticles were formed by combining cationic PBAEs with anionic DNA or siRNA and allowing for self-assembly. Gold nanoparticles (AuNPs) were synthesized via a modified Frens method. Multilayer theranostic nanoparticles were designed following Figure 2. Fluorescence microscopy and flow cytometry were performed over time to measure transfection efficacy of reporter genes in GB319 human glioblastoma cells. siRNA-mediated gene knockdown was performed in constitutively eGFP positive GB319s. Cellular viability was measured by the CellTiter96® assay. In vivo evaluation of non-viral gene delivery nanoparticles was performed in an orthotopic patient-derived glioblastoma model in male nude athymic mice[2]. Figure 2. The layer-by-layer (LbL) fabrication process to create inorganic/polymeric hybrid nanoparticles. Results and Discussion: Non-bioreducible PBAE nanoparticles were found to be highly effective for DNA delivery, reaching 90% transfection efficacy without causing non-specific cytotoxicity. Certain bioreducible PBAE nanoparticles were found to be relatively ineffective for DNA delivery, but highly effective for siRNA delivery. These bioreducible nanoparticles led to 90% gene knockdown also without causing non-specific cytotoxicity. Polymers with increased hydrophobicity were found to be more effective for both DNA and siRNA delivery. When administered in vivo, 447/DNA nanoparticles successfully transfected the patient-derived glioblastoma cells in the mouse model and also demonstrated tumor-cell specific transfection. To enable kinetic control of exogenous gene expression of multiple genes, layer-by-layer (LbL) inorganic/polymeric hybrid nanoparticles were successfully fabricated. The zeta potential of the LbL inorganic/polymeric nanoparticles reversed at each of the 7 stages of layering, confirming that the coatings of each polyelectrolyte layer were achieved. The outer eGFP DNA layer of the LbL inorganic/polymeric nanoparticles transfected highly at day 2 and this level of gene expression persisted until day 9, when it then decreased over time (Figure 3). In contrast, the inner dsRed DNA layer had low expression initially that steadily increased to a maximum at day 9. Temporal control of multi-gene delivery was achieved by the physical placement of these different plasmids within the LbL layers and by biomaterial properties. Figure 3. Normalized transfection efficacies of inorganic/polymeric hybrid nanoparticles demonstrating temporal control of exogenous gene expression in human glioblastoma cells. Conclusion: Using a polymer library approach we were able to achieve high non-viral DNA delivery with low cytotoxicity as well as high siRNA knockdown with low cytotoxicity to human brain cancer cells. Certain polymer features, including hydrophobicity and mode of degradation, were key parameters for the effective nanomaterials. In addition, these nanoparticles showed efficacy in vivo in a human glioblastoma mouse model. Using an LbL approach, we were able to successfully develop a method to electrostatically coat inorganic theranostic nanoparticles that can load two different types of plasmids and deliver them with temporal control. National Institutes of Health (R01EB016721)

Amoxicillin functionalized gold nanoparticles reverts MRSA resistance

In this study, we have described the biosynthesis of biocompatible gold nanoparticles (GNPs) from aqueous extract of the aerial parts of a pteridophyte, “Adiantum philippense” by microwave irradiation and its surface functionalization with broad spectrum beta lactam antibiotic, amoxicillin (Amox). The functionalization of amoxicillin on GNPs (GNP-Amox) was carried out via electrostatic interaction of protonated amino group and thioether moiety mediated attractive forces. The synthesized GNPs and GNP-Amox were physicochemically characterized. UV–Vis spectroscopy, Zeta potential, XRD, FTIR and SERS (surface enhanced raman spectra) results confirmed the loading of Amox into GNPs. Loading of Amox to GNPs reduce amoxicillin cytotoxicity, whereas GNPs were found to be nontoxic to mouse fibroblast cell line (L929) as evident from MTT and acridine orange/ethidium bromide (AO/EtBr) live/dead cell assays. The GNP-Amox conjugates demonstrated enhanced broad-spectrum bactericidal activity against both Gram-positive and Gram-negative bacteria. Furthermore, in-vitro and in-vivo assays of GNP-Amox revealed potent anti-MRSA activity and improved the survival rate. This indicates the subversion of antibiotic resistance mechanism by overcoming the effect of high levels of β-lactamase produced by methicillin resistant Staphylococcus aureus (MRSA). Taken together, this study demonstrates the positive attributes from GNP-Amox conjugates as a promising antibacterial therapeutic agent against MRSA as well as other pathogens.

Synthesis of novel galactose functionalized gold nanoparticles and its radiosensitizing mechanism.

BackgroundBiocompatible gold nanoparticles (GNPs) are potentially practical and efficient agents in cancer radiotherapy applications. In this study, we demonstrated that GNPs can significantly modulate irradiation response of hepatocellular carcinoma cells in vitro and investigated the underlying mechanisms. We co-grafted galactose (GAL) targeting hepatocyte specific asialoglycoprotein receptor and Polyethylene Glycol (PEG) onto GNPs surfaces to increase GNPs targeting specificity and stability.ResultsThis novel GAL-PEG-GNPs and bare GNPs show similar appearance and cytotoxicity profiles, while more GAL-PEG-GNPs can be effectively uptaken and could enhance cancer cell killing.ConclusionGAL-PEG-GNPs have better radiosensitization to HepG2. The sensitization mechanism of GAL-PEG-GNPs is related to the apoptotic gene process activated by generation of a large amount of free radicals induced by GNPs.

Green synthesis of gold nanoparticles using Pterocarpus marsupium: Characterization and biocompatibility studies

ABSTRACTThe present study aims to synthesize gold nanoparticles (GNPs) by green method using Pterocarpus marsupium and to study the effect of various parameters like stirring, pH, and temperature on morphology and stability of GNPs. The study was further extended to evaluate the role of antioxidants in the green synthesis of GNPs. Formation of GNPs was confirmed by visual color change from colorless to wine red and UV-Visible spectrophotometry. Particle size was found to be in the range of 72–85 nm. There was no significant difference in the size and shape of GNPs prepared by different conditions; however, difference in zeta potential suggested difference in stability. GNPs prepared by heating (40°C) were comparatively more stable than GNPs synthesized at different conditions. Fourier-transform infrared spectroscopy suggests the presence of flavonoids and polyphenols. X-ray diffraction studies revealed the crystalline nature of GNPs, while transmission electron microscopy studies suggested mixed morphology of GNPs. In vitro stability studies revealed that GNPs were stable in all conditions except at lower pH and 5% NaCl solution. Synthesized GNPs were found biocompatible in nature. This ecofriendly method for the synthesis of GNPs is rapid and easy which yields stable and biocompatible GNPs which could be used for many biomedical applications.

Natural polysaccharide functionalized gold nanoparticles as biocompatible drug delivery carrier

Biocompatibility is one of the major concerns with inorganic nanoparticles for their applications as drug delivery system. Natural compounds such as sugars, hydrocolloids and plant extracts have shown potential for the green synthesis of biocompatible gold nanoparticles. In this study, we report the synthesis of gum karaya (GK) stabilized gold nanoparticles (GKNP) and the application of prepared nanoparticles in the delivery of anticancer drugs. GKNP were characterized using different analytical techniques. GKNP exhibited high biocompatibility during cell survival study against CHO normal ovary cells and A549 human non-small cell lung cancer cells and during hemolytic toxicity studies. Gemcitabine hydrochloride (GEM), an anticancer drug, was loaded on the surface of nanoparticles with 19.2% drug loading efficiency. GEM loaded nanoparticles (GEM-GNP) showed better inhibition of growth of cancer cells in anti-proliferation and clonogenic assays than native GEM. This effect was correlated with higher reactive oxygen species generation by GEM-GNP in A549 cells than native GEM. In summary, GK has significant potential in the synthesis of biocompatible gold nanoparticles that could be used as prospective drug delivery carrier for anticancer drugs.

A green chemistry approach for the synthesis of gold nanoconjugates that induce the inhibition of cancer cell proliferation through induction of oxidative stress and their in vivo toxicity study.

In this paper, we report the synthesis of gold nanoconjugates (b-Au-LM) using the aqueous leaf extract of Lantana montevidensis (LM), a naturally available medicinal plant. The biosynthesized b-Au-LM was biocompatible in both in vitro and in vivo systems. However, the LM extract as well as b-Au-LM exhibited significant inhibition of the proliferation of cancer cells. Interestingly, b-Au-LM showed enhanced anti-cancer activity compared to the pristine LM extract. Generation of reactive oxygen species (ROS) and oxidative stress, which triggered the upregulation of caspase-3, might be the plausible reason for anti-cancer activity. Cell cycle analysis demonstrated G2/M (in A549 cells) or Sub-G1 (in MCF-7) cell cycle arrest, which might lead to apoptosis. Together, the results support the future therapeutic application of an in situ biosynthesized gold nanoconjugates based drug delivery system (b-Au-LM) towards cancer therapy and other biomedical applications.

Small, stable and biocompatible gold nanoparticles capped with a β-cyclodextrin polymer

Gold nanoparticles capped with a β-cyclodextrin epichlorohydrin polymer resulted to be smaller than 5 nm, stable in physiological fluid and biocompatible, features that denote their capability as scaffold for future applications in nanomedicine.

Green synthesis of biocompatible carboxylic curdlan-capped gold nanoparticles and its interaction with protein.

This study demonstrates a facile, green strategy for the preparation of gold nanoparticles (AuNPs) from chloroauric acid (HAuCl4) using carboxylic curdlan (Cc) as both reducing and stabilizing agent. The as-prepared AuNPs are characterized by UV-vis spectroscopy, high resolution transmission electron microscopy, X-ray diffraction, energy dispersive X-ray spectrometry and Fourier transform infrared spectroscopy. The results indicated that the particle size of the AuNPs changes with variations in the reaction time and concentrations of Cc and HAuCl4. The spherical AuNPs are well dispersed, exhibiting high stability even after six months storage. The carboxylic groups (COO(-)) in the Cc molecules tend to adsorb and stabilize the surface of the AuNPs. The interaction between BSA and the Cc-capped AuNPs was investigated using fluorescence and circular dichroism spectroscopies. The results indicated that the BSA molecules adsorb on the surface of the AuNPs, without significant change in its helical structure even after conjugation with the AuNPs.

A green chemistry approach for synthesizing biocompatible gold nanoparticles.

Gold nanoparticles (AuNPs) are a fascinating class of nanomaterial that can be used for a wide range of biomedical applications, including bio-imaging, lateral flow assays, environmental detection and purification, data storage, drug delivery, biomarkers, catalysis, chemical sensors, and DNA detection. Biological synthesis of nanoparticles appears to be simple, cost-effective, non-toxic, and easy to use for controlling size, shape, and stability, which is unlike the chemically synthesized nanoparticles. The aim of this study was to synthesize homogeneous AuNPs using pharmaceutically important Ganoderma spp. We developed a simple, non-toxic, and green method for water-soluble AuNP synthesis by treating gold (III) chloride trihydrate (HAuCl4) with a hot aqueous extract of the Ganoderma spp. mycelia. The formation of biologically synthesized AuNPs (bio-AuNPs) was characterized by ultraviolet (UV)-visible absorption spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray (EDX), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Furthermore, the biocompatibility of as-prepared AuNPs was evaluated using a series of assays, such as cell viability, lactate dehydrogenase leakage, and reactive oxygen species generation (ROS) in human breast cancer cells (MDA-MB-231). The color change of the solution from yellow to reddish pink and strong surface plasmon resonance were observed at 520 nm using UV-visible spectroscopy, and that indicated the formation of AuNPs. DLS analysis revealed the size distribution of AuNPs in liquid solution, and the average size of AuNPs was 20 nm. The size and morphology of AuNPs were investigated using TEM. The biocompatibility effect of as-prepared AuNPs was investigated in MDA-MB-231 breast cancer cells by using various concentrations of AuNPs (10 to 100 μM) for 24 h. Our findings suggest that AuNPs are non-cytotoxic and biocompatible. To the best of our knowledge, this is the first report to describe the synthesis of monodispersed, biocompatible, and soluble AuNPs with an average size of 20 nm using Ganoderma spp. This study opens up new possibilities of using an inexpensive and non-toxic mushroom extract as a reducing and stabilizing agent for the synthesis of size-controlled, large-scale, biocompatible, and monodispersed AuNPs, which may have future diagnostic and therapeutic applications.

Delivery of antiviral small interfering RNA with gold nanoparticles inhibits dengue virus infection in vitro.

Dengue virus (DENV) infection in humans can cause flu-like illness, life-threatening haemorrhagic fever or even death. There is no specific anti-DENV therapeutic or approved vaccine currently available, partially due to the possibility of antibody-dependent enhancement reaction. Small interfering RNAs (siRNAs) that target specific viral genes are considered a promising therapeutic alternative against DENV infection. However, in vivo, siRNAs are vulnerable to degradation by serum nucleases and rapid renal excretion due to their small size and anionic character. To enhance siRNA delivery and stability, we complexed anti-DENV siRNAs with biocompatible gold nanoparticles (AuNPs) and tested them in vitro. We found that cationic AuNP-siRNA complexes could enter Vero cells and significantly reduce DENV serotype 2 (DENV-2) replication and infectious virion release under both pre- and post-infection conditions. In addition, RNase-treated AuNP-siRNA complexes could still inhibit DENV-2 replication, suggesting that AuNPs maintained siRNA stability. Collectively, these results demonstrated that AuNPs were able to efficiently deliver siRNAs and control infection in vitro, indicating a novel anti-DENV strategy.

68Ga-Labeled Gold Glyconanoparticles for Exploring Blood–Brain Barrier Permeability: Preparation, Biodistribution Studies, and Improved Brain Uptake via Neuropeptide Conjugation

New tools and techniques to improve brain visualization and assess drug permeability across the blood-brain barrier (BBB) are critically needed. Positron emission tomography (PET) is a highly sensitive, noninvasive technique that allows the evaluation of the BBB permeability under normal and disease-state conditions. In this work, we have developed the synthesis of novel water-soluble and biocompatible glucose-coated gold nanoparticles (GNPs) carrying BBB-permeable neuropeptides and a chelator of the positron emitter (68)Ga as a PET reporter for in vivo tracking biodistribution. The small GNPs (2 nm) are stabilized and solubilized by a glucose conjugate. A NOTA ligand is the chelating agent for the (68)Ga, and two related opioid peptides are used as targeting ligands for improving BBB crossing. The radioactive labeling of the GNPs is completed in 30 min at 70 °C followed by purification via centrifugal filtration. As a proof of principle, a biodistribution study in rats is performed for the different (68)Ga-GNPs. The accumulation of radioactivity in different organs after intravenous administration is measured by whole body PET imaging and gamma counter measurements of selected organs. The biodistribution of the (68)Ga-GNPs varies depending on the ligands, as GNPs with the same gold core size show different distribution profiles. One of the targeted (68)Ga-GNPs improves BBB crossing near 3-fold (0.020 ± 0.0050% ID/g) compared to nontargeted GNPs (0.0073 ± 0.0024% ID/g) as measured by dissection and tissue counting.