Cationic Gold Nanoparticles Research Articles

Preparation of fusion materials based on ionic liquids and cationic gold nanoparticles

Fusion materials based on cationic gold nanoparticles mixed with ionic liquids were prepared. An anion exchange of the surface-capping ligand on the gold nanoparticles from a halogen anion to bis(trifluoromethanesulfonyl)amide (Tf2N) in an aqueous solution afforded nanoparticles showing infinite miscibility with Tf2N-based ionic liquids. The thermal decomposition temperature of the gold nanoparticle was elevated by 100 °C after the anion-exchange process. The ionic liquid-like structure of the surface-capping ligand with Tf2N anions led to a glassy solid material with a densely packed assembly of nanoparticles, in which a portion of nanoparticles formed superlattices. A fusion material of ionic liquid and gold nanoparticles with a gold content as high as 40 wt% was obtained by the co-solvent evaporation method using acetone. The stable dispersion of gold nanoparticles in the fusion materials with a high gold content was confirmed by the clear appearance of the plasmon absorption of gold nanoparticles in an optical microscopic image, as well as in an absorption spectrum. The use of an ionic liquid-based monomer yielded a gold nanoparticle–ionic liquid polymer composite, in which the gold nanoparticles showed a high thermal stability. Gold nanoparticles capped with a simplified ionic liquid-like ligand were prepared, which were incorporated into the fusion materials with ionic liquids at concentrations of up to 40 wt% of inorganic content. The fusion material of gold nanoparticles with an ionic liquid monomer was readily converted into a polymeric composite, in which gold nanoparticles showed high thermal stability.

Direct cytosolic delivery of siRNA using nanoparticle-stabilized nanocapsules.

The use of nanoparticle-stabilized nanocapsules (NPSCs) for the direct cytosolic delivery of siRNA is reported. In this approach, siRNA is complexed with cationic arginine-functionalized gold nanoparticles by electrostatic interactions, with the resulting ensemble self-assembled onto the surface of fatty acid nanodroplets to form a NPSC/siRNA nanocomplex. The complex rapidly delivers siRNA into the cytosol through membrane fusion, a mechanism supported by cellular uptake studies. Using destabilized green fluorescent protein (deGFP) as a target, 90% knockdown was observed in HEK293 cells. Moreover, the delivery of siRNA targeting polo-like kinase 1 (siPLK1) efficiently silenced PLK1 expression in cancer cells with concomitant cytotoxicity.

Accurate determination of the size distribution for polydisperse, cationic metallic nanomaterials by asymmetric-flow field flow fractionation

In this work we have developed and validated a methodology for determining the size distribution in polydisperse cationic nanoparticle (NP) samples using asymmetric-flow field flow fractionation (A4F), where known compositional influence of previously used calibrants was mitigated. Both the accurate determination of NP size distributions, in general, and the evaluation of cationic species with A4F have proved to be persistent analytical challenges, especially for strong, optically absorbing metallic NPs. In order to overcome these challenges, highly uniform and monomodal cetyl trimethylammonium bromide (CTAB)-stabilized SeNPs were prepared through a facile synthetic procedure and were further validated as an appropriate calibrant for cationic gold NPs based on their inherent optical properties and (nearly) identical retention behavior. Due to the uniform retention behavior resulting from the NP coating and narrow distribution (σ d ≪ diameter) of the calibrant, the contributions from sample polydispersity and instrumental broadening of the theoretical plate height, H, could be isolated and the size distribution determined. Although this has been demonstrated previously for macromolecules, to our knowledge the size distribution has not been reported and validated for NP analytes. Implementation of the calibrant in a polydisperse CTAB-coated AuNP sample demonstrates the capabilities of the current method and could be easily extended to other systems. Overall, the necessity of robust methods for size distribution determination are currently addressed that incorporate appropriate calibrants when light scattering methods are intractable, providing an alternative method in systems that are difficult with traditional microscopy approaches.

Surface-enhanced Raman spectroscopy of the endothelial cell membrane.

We applied surface-enhanced Raman spectroscopy (SERS) to cationic gold-labeled endothelial cells to derive SERS-enhanced spectra of the bimolecular makeup of the plasma membrane. A two-step protocol with cationic charged gold nanoparticles followed by silver-intensification to generate silver nanoparticles on the cell surface was employed. This protocol of post-labelling silver-intensification facilitates the collection of SERS-enhanced spectra from the cell membrane without contribution from conjugated antibodies or other molecules. This approach generated a 100-fold SERS-enhancement of the spectral signal. The SERS spectra exhibited many vibrational peaks that can be assigned to components of the cell membrane. We were able to carry out spectral mapping using some of the enhanced wavenumbers. Significantly, the spectral maps suggest the distribution of some membrane components are was not evenly distributed over the cells plasma membrane. These results provide some possible evidence for the existence of lipid rafts in the plasma membrane and show that SERS has great potential for the study and characterization of cell surfaces.

Keplerate cluster (Mo-132) mediated electrostatic assembly of nanoparticles

The electrostatic assembly between a series of differently charged Mo-132-type Keplerates present in the compounds (NH4)42[{(MoVI)MoVI5O21(H2O)6}12 {MoV2O4(CH3COO)}30].ca. {300 H2O+10 CH3COONH4} (Mo-132a), (NH4)72−n[{(H2O)81−n+(NH4)n} {(MoVI)MoVI5O21(H2O)6}12 {MoV2O4(SO4)}30].ca. 200 H2O (Mo-132b), and Na10(NH4)62[{(MoVI)MoVI5O21(H2O)6}12 {MoV2O4(HPO4)}30]. ca. {300H2O+2Na++2NH4++4H2PO4−} (Mo-132c) with cationic gold nanoparticles (AuNPs) was investigated for the first time. The rapid electrostatic assembly from nanoscopic entities to micron scale aggregates was observed upon precipitation, which closely matched the point of aggregate electroneutrality. Successful assembly was demonstrated using UV–vis, DLS, TEM, and zeta-potential analysis. Results indicate that the point at which precipitation occurs is related to charge balance or electroneutrality, and that counterions at both the Mo-132 and AuNP play a significant role in assembly.

Surface chemistry of gold nanoparticles mediates their exocytosis in macrophages.

Significant quantities of synthetic nanoparticles circulating in the body are cleared and retained for long periods of time in the resident macrophages of the mononuclear phagocytic system (MPS), increasing the likelihood of nanoparticle-mediated chronic toxicity. To date, there has been limited effort to understand how these nanoparticles leave the macrophages. Here, we demonstrate that the native surface chemistries of gold nanoparticles (GNPs) and their subsequent opsonization by serum proteins play critical roles in the exocytosis patterns in macrophages. The cationic GNPs were retained in the cells for a relatively long time, likely due to their intracellular agglomeration. In contrast, the PEGylated GNPs migrated in the cytoplasm in the form of individual particles and exited the cells rapidly because the PEG coating mitigated interactions between GNPs and intracellular proteins. Additionally, their exocytosis pattern was not significantly governed by the size, particularly in the range from 10 to 40 nm. These results suggest that systemic excretion and toxicity of nanoparticles cleared in the MPS could be modulated by engineering their surface chemistry.

Biological synthesis of cationic gold nanoparticles and binding of plasmid DNA

Nanobiotechnology is the development of eco-friendly experimental processes for the synthesis of nanomaterials. The present work focuses on synthesis of cationic gold nanoparticles (C-GNPs) for biological applications, especially in gene and drug delivery studies. A biosynthesis methodology has been developed for the functionalization of gold nanoparticles to cationic nature. The synthesis of C-GNPs was done by using peanut leaf extract in the presence of cysteamine. The formed C-GNPs were characterized by using UV–visible spectroscopy (UV–vis), the particles sizes and shapes were confirmed by a Transmission electron microscope (TEM) and crystallinity of C-GNPs was characterized by diffraction. The binding of plasmid DNA on the C-GNPs was confirmed by agarose gel electrophoresis.

Probing the protein–nanoparticle interface: the role of aromatic substitution pattern on affinity

A new class of cationic gold nanoparticles (NPs) has been synthesised bearing benzyl moieties featuring –NO2 and –OMe groups to investigate the regioisomeric control of aromatic NP–protein recognition. In general, NPs bearing electron-withdrawing groups demonstrated higher binding affinities towards green fluorescent protein (GFP) than NPs bearing electron-donating groups. Significantly, a ∼7.5- and ∼4.3-fold increase in binding with GFP was observed for –NO2 groups in meta-position and para-position, respectively, while ortho-substitution showed binding similar to the unsubstituted ring. These findings demonstrated that the NP–protein interaction can be controlled by tuning the spatial orientation and the relative electronic properties of the aromatic substituents. This improved biomolecular recognition provides opportunities for enhanced biosensing and functional protein delivery to the cells.

Fabrication of Multiresponsive Bioactive Nanocapsules through Orthogonal Self‐Assembly

AbstractMultifunctional self‐assembled systems present platforms for fundamental research and practical applications as they provide tunability of structure, functionality, and stimuli responsiveness. Pragmatic structures for biological applications have multiple design requirements, including control of size, stability, and environmental response. Here we present the fabrication of multifunctional nanoparticle‐stabilized capsules (NPSCs) by using a set of orthogonal supramolecular interactions. In these capsules, fluorescent proteins are attached to quantum dots through polyhistidine coordination. These anionic assemblies interact laterally with cationic gold nanoparticles that are anchored to the fatty acid core through guanidinium–carboxylate interactions. The lipophilic core then provides a reservoir for hydrophobic endosome‐disrupting agents, thereby generating a system featuring stimuli‐responsive release of a payload into the cytosol with fluorescence monitoring.

Fabrication of multiresponsive bioactive nanocapsules through orthogonal self-assembly.

Multifunctional self-assembled systems present platforms for fundamental research and practical applications as they provide tunability of structure, functionality, and stimuli responsiveness. Pragmatic structures for biological applications have multiple design requirements, including control of size, stability, and environmental response. Here we present the fabrication of multifunctional nanoparticle-stabilized capsules (NPSCs) by using a set of orthogonal supramolecular interactions. In these capsules, fluorescent proteins are attached to quantum dots through polyhistidine coordination. These anionic assemblies interact laterally with cationic gold nanoparticles that are anchored to the fatty acid core through guanidinium-carboxylate interactions. The lipophilic core then provides a reservoir for hydrophobic endosome-disrupting agents, thereby generating a system featuring stimuli-responsive release of a payload into the cytosol with fluorescence monitoring.

Effect of Charge Regulation and Ion–Dipole Interactions on the Selectivity of Protein–Nanoparticle Binding

We investigate the role of different mesoscopic interactions (Coulomb, charge regulation, and ion-dipole "surface patch" effects) on the binding of bovine serum albumin (BSA) and β-lactoglobulin (BLG) to a cationic gold nanoparticle (TTMA+). The results demonstrate that the charge-regulation mechanism plays a vital role for selectivity of protein-nanoparticle complexation at low salt concentration. At slightly higher ionic strengths, charge-dipole effects are the dominating driving force. Thus, very small variations in salt concentration strongly influence the origin of complexation.

A colorimetric aptamer biosensor based on cationic polymer and gold nanoparticles for the ultrasensitive detection of thrombin

A colorimetric assay for the ultrasensitive determination of thrombin based on cationic polymer and gold nanoparticles was presented, in which unmodified gold nanoparticles (AuNPs) was used as probes and 21-mer thrombin-binding aptamer (TBA) as sensing elements. Upon the addition of thrombin, TBA interacted specifically with thrombin to form a G-quadruplex structure. As a result, the conformation change facilitated the cationic polymer, poly(diallyldimethylammonium chloride) (PDDA)-induced AuNP aggregation. Thus, the visible change in color from wine-red to blue–purple was readily seen by the naked eye. The colorimetric sensor could detect thrombin down to 1pM with high selectivity in the presence of other interferring proteins. Furthermore, the assay was successfully employed to determine thrombin in human serum sample, which suggested its great potential for diagnostic purposes.

Optimizing the selective recognition of protein isoforms through tuning of nanoparticle hydrophobicity.

We demonstrate that ligand hydrophobicity can be used to increase affinity and selectivity of binding between monolayer-protected cationic gold nanoparticles and β-lactoglobulin protein isoforms containing two amino acid mutations.

Cell Membranes Open “Doors” for Cationic Nanoparticles/Biomolecules: Insights into Uptake Kinetics

Cationic nanoparticles (NPs) and cell-penetrating peptides (CPPs) can enter cells in an energy-independent fashion, escaping the traditional endocytosis route, which is known as direct translocation. This unconventional entry, usually complementary to endocytosis, features rapid uptake and thus makes both cationic NPs and CPPs fascinating intracellular delivery agents. However, the mechanisms of the direct translocation of both cationic NPs and CPPs across cell membranes into the cytosol are not understood. Moreover, the relationship between direct translocation and endocytosis is also unclear. Here, using coarse-grained molecular dynamics simulations we show that a model cell membrane generates a nanoscale hole to assist the spontaneous translocation of cationic gold nanoparticles (AuNPs) as well as HIV-1 Tat peptides to the cytoplasm side under a transmembrane (TM) potential. After translocation, the AuNPs/Tat peptides move freely in the "cytoplasm" region and the membrane reseals itself within a microsecond, while the TM potential is strongly diminished. Furthermore, we show that the shape of the cationic object is crucial in determining if it can translocate or not across. The results provide insights into the uptake kinetics of cationic NPs/CPPs, which features the relationship between direction translocation and endocytosis. The mechanism put forward here establishes fundamental principles of the intracellular delivery of cationic nanocarriers.

Direct detection of hyaluronidase in urine using cationic gold nanoparticles: A potential diagnostic test for bladder cancer

Hyaluronidase (HAase) was reported as a urinary marker of bladder cancer. In this study, a simple colorimetric gold nanoparticle (AuNP) assay was developed for rapid and sensitive detection of urinary HAase activity. Charge interaction between polyanionic hyaluronic acid (HA) and cationic AuNPs stabilized with cetyl trimethyl ammonium bromide (CTAB) led to formation of gold aggregates and a red to blue color shift. HAase digests HA into small fragments preventing the aggregation of cationic AuNPs. The nonspecific aggregation of AuNPs in urine samples was overcome by pre-treatment of samples with the polycationic chitosan that was able to agglomerate all negatively charged interfering moieties before performing the assay. The developed AuNP assay was compared with zymography for qualitative detection of urinary HAase activity in 40 bladder carcinoma patients, 11 benign bladder lesions patients and 15 normal individuals, the assay sensitivity was 82.5% vs. 65% for zymography, while the specificity for both assays was 96.1%. The absorption ratio, A530/A620 of the reacted AuNP solution was used to quantify the HAase activity. The best cut off value was 93.5μU/ng protein, at which the sensitivity was 90% and the specificity was 80.8%.The developed colorimetric AuNP HAase assay is simple, inexpensive, and can aid noninvasive diagnosis of bladder cancer.

Detection of unamplified HCV RNA in serum using a novel two metallic nanoparticle platform

The unique properties of metallic nanoparticles have enabled their utilization in biosensing applications. A novel assay for the detection of hepatitis C virus (HCV) RNA in serum specimens has been developed using magnetic nanoparticles and unmodified cationic gold nanoparticles (AuNPs). HCV RNA was extracted using magnetic nanoparticles functionalized with an oligonucleotide specific to HCV RNA. Extracted RNA is reacted with oligonucleotide sequence specific for HCV RNA in presence of unmodified cationic AuNPs. In positive samples, AuNPs are aligned onto the phosphate backbone of the RNA and their aggregation changes the solution color from red to blue. In the absence of target, solution color remains red. The assay has been tested on 50 serum clinical samples (25 HCV positive and 25 controls). The dual nanoparticles assay detected HCV RNA in serum and generated comparable results to real-time PCR. The assay had specificity and a sensitivity of 96% and 96.5%, respectively, and a detection limit of 15 IU/mL. The developed colorimetric dual nanoparticles HCV RNA assay is simple and inexpensive and can be used for rapid detection of unamplified HCV RNA in serum. Similar sensing platforms can be developed to detect other nucleic acid targets.

Synthesis of Anionic Sulfonate-functionalized Conducting Polymer Nanotubes and Selective Confinement of Cationic Gold Nanoparticles in Their Inner Cavities via Electrostatic Interaction

Abstract New sulfonate-functionalized conducting polythiophene nanotubes were synthesized and easily dispersed in water without them aggregating. The positively charged Au nanoparticles with viologen were selectively attached to the inner surfaces of their negatively charged polythiophene nanotubes via an interfacial electrostatic interaction.

Rapid colorimetric detection of illegal cooking oils based on phase transfer technology

In recent years, illegal cooking oil incident led to the serious food safety risks and the negative social repercussions. In this paper, the copper ions and the cationic gold nanoparticles modified by poly(diallyl dimethylammonium) chloride (PDDA) were used as the recognition probes. Two rapid and convenient colorimetric detection methods of illegal cooking oils based on phase transfer technology were established. The results showed that qualified cooking oil mixed with 2.8% of the illegal cooking oil could be detected, and more than 5% of the illegal cooking oil could be detected accurately by naked-eye. These methods were applied in blind test for total of 235 samples; the results showed that the accurate rates of the blind tests were 95.7%. This work would be helpful for the rapid and on-site detection of illegal cooking oils.

Synthesis and Enhanced Colloidal Stability of Cationic Gold Nanoparticles using Polyethyleneimine and Carbon Dioxide

Employing green methods in the design and synthesis of functionalized metallic nanoparticles poses significant challenges in terms of maintaining product integrity (size, shape, dispersity, and colloidal stability). In this study, the direct synthesis of cationic gold nanoparticles (GNPs) capped by low molecular weight (Mw ∼ 600) polyethylenimine was investigated. Specifically, three separate HAuCl4 reduction pathways were used to produce robust GNPs with sizes ranging from 4 to 20 nm in diameter with excellent size control. The inclusion of carbon dioxide as a nontoxic, nonflammable, and inexpensive component led to decreases in particle size and an increase in the colloidal stability of the GNPs. Furthermore, the thermally reversible reaction of CO2 with amines provides means to control the solvent pH through carbamate structures and, hence, the controllable formation of particle aggregates. The effects of pH, PEI concentration, and reduction method on the particle core size and stability were determine...

A colorimetric aptasensor for the diagnosis of malaria based on cationic polymers and gold nanoparticles

Malaria, a major burden of disease caused by parasites of the genus Plasmodium, is widely spread in tropical and subtropical regions. Here, we have successfully developed a diagnostic technique for malaria. The proposed method is based on the interaction among the Plasmodium lactate dehydrogenase (pLDH), which is a biomarker for malaria, and pL1 aptamer against Plasmodium vivax lactate dehydrogenase (PvLDH) and Plasmodium falciparum lactate dehydrogenase (PfLDH). In addition, the cationic polymers, poly(diallyldimethylammonium chloride) (PDDA) and poly(allylamine hydrochloride) (PAH), aggregate gold nanoparticles (AuNPs) that should be possible to observe the change in color from red to blue, which depends on the concentration of pLDH. Using this aptasensor, pLDH proteins were successfully detected with low detection limits. Moreover, the specificity test proved that the aptasenor is very specific in targeting proteins over other interfering proteins. In addition, the pLDH from infected blood samples of the two main species of malaria were also detected. The limits of detection for P. vivax were determined as 80 parasites/μl for PDDA and 74 parasites/μl for PAH. The aptasenor has great advantages that can simply and rapidly diagnose malaria. Thus, the developed aptasensor for detection of pLDH can offer an effective and sensitive diagnosis of malaria.