Polymer-coated Gold Nanoparticles Research Articles

Construction of folate-targeted delivery of polymer-coated gold nanoparticles: investigation of anticancer activity and apoptosis induction in parotid gland carcinoma

Construction of folate-targeted delivery of polymer-coated gold nanoparticles: investigation of anticancer activity and apoptosis induction in parotid gland carcinoma

Fluorine-modified polymers reduce the adsorption of immune-reactive proteins to PEGylated gold nanoparticles.

Aim: To investigate the influence of fluorine in reducing the adsorption of immune-reactive proteins onto PEGylated gold nanoparticles. Methods: Reversible addition fragmentation chain transfer polymerization, the Turkevich method and ligand exchange were used to prepare polymer-coated gold nanoparticles. Subsequent in vitro physicochemical and biological characterizations and proteomic analysis were performed. Results: Fluorine-modified polymers reduced the adsorption of complement and other immune-reactive proteins while potentially improving circulatory times and modulating liver toxicity by reducing apolipoprotein E adsorption. Fluorine actively discouraged phagocytosis while encouraging the adsorption of therapeutic targets, CD209 and signaling molecule calreticulin. Conclusion: This study suggests that the addition of fluorine in the surface coating of nanoparticles could lead to improved performance in nanomedicine designed for the intravenous delivery of cargos.

5-Fluorouracil-Impregnated PLGA Coated Gold Nanoparticles for Augmented Delivery to Lung Cancer: In Vitro Investigations.

The study aimed to investigate the augmented cytotoxic effects of polymer-coated (polylactic- co-glycolic acid-PLGA) gold nanoparticles (GNPs) carrying 5-fluorouracil (5-FU) in the management of lung cancer. In this study, several formulations were prepared using a double emulsion (water-oil-water) method and evaluated for drug release behavior, compatibility, cell line toxicity (A549), and apoptosis assessment. Characterization results showed spherical polydispersed particles with size 29.11-178.21 nm, polydispersity index (PDI) 0.191-292, and zeta potential (ZP) 11.19-29.21 (-mV), respectively. Compared to others, the optimized polymer-coated 5-FU loaded gold nanoparticles (PFGNPs) illustrated a maximum drug loading (93.09±10.75%). The percent cumulative drug release of polymer-coated 5-FU loaded nanoparticles (PFNPs), 5-FU loaded gold nanoparticles (FGNPs), (PFGNPs) and 5-FU solution were 47.87±1.5, 41.09±1.8, 56.31±1.05, and 98.8±4.2%, respectively, over 10 h. following zero-order release kinetics (except 5-FU solution). From the MTT results, the cytotoxic effect of PFGNPs on the A549 cells was 82.89% compared to the 5-FU solution (74.91 %). EGFR and KRAS gene expression analysis under the influence of PFNPs, FGNPs, PFGNPs, and 5-FU was studied and observed maximum potency for PFNPs. PLGA coated biogenic gold nanoparticles have a combined effect to achieve high drug loading, sustained delivery, improved efficacy, and enhanced permeation. Conclusively, the approach may be promising to control lung cancer with reduced toxicity and improved efficacy.

Scattering-type Scanning Near-Field Optical Microscopy of Polymer-Coated Gold Nanoparticles.

Scattering-type scanning near-field optical microscopy (s-SNOM) has emerged over the past years as a powerful characterization tool that can probe important properties of advanced materials and biological samples in a label-free manner, with spatial resolutions lying in the nanoscale realm. In this work, we explore such usefulness in relationship with an interesting class of materials: polymer-coated gold nanoparticles (NPs). As thoroughly discussed in recent works, the interplay between the Au core and the polymeric shell has been found to be important in many applications devoted to biomedicine. We investigate bare Au NPs next to polystyrenesulfonate (PSS) and poly(diallyldimethylammonium chloride) (PDDA) coated ones under 532 nm laser excitation, an wavelength matching the surface plasmon band of the custom-synthesized nanoparticles. We observe consistent s-SNOM phase signals in the case of bare and shallow-coated Au NPs, whereas for thicker shell instances, these signals fade. For all investigated samples, the s-SNOM amplitude signals were found to be very weak, which may be related to reduced scattering efficiency due to absorption of the incident beam. We consider these observations important, as they may facilitate studies and applications in nanomedicine and nanotechnology where the precise positioning of polymer-coated Au NPs with nanoscale resolution is needed besides their dielectric function and related intrinsic optical properties, which are also quantitatively available with s-SNOM.

Conjugation of Polymer-Coated Gold Nanoparticles with Anti-EGFR Antibodies for Enhanced Radiation Therapy

Conjugation of Polymer-Coated Gold Nanoparticles with Anti-EGFR Antibodies for Enhanced Radiation Therapy

Polymer-coated gold nanoparticles and polymeric nanoparticles as nanocarrier of the BP100 antimicrobial peptide through a lung surfactant model

Pneumonia is caused by microorganisms that settle in the lungs, which may reach the pulmonary alveoli and cause respiratory failure. Antibiotic treatments are the most used, although their use may not be efficient due to bacterial resistance. The antimicrobial peptide BP100 is a promising candidate for a new antibiotic due to its low susceptibility to bacterial resistance. It can be most effective when carried with gold nanoparticles (AuNPs) and polymer coatings for topical use. The goal of this work is to evaluate the effect of the transposition of the BP100 peptide carried on a gold nanoparticle coated with three types of polymers (polyethylene glycol (PEG), polystyrene (PS) and polyethylene glycol-block-polystyrene (PEG-b-PS)) using a lung surfactant (LS) model. The Gibbs free energies for nanoparticle transpositions are performed using coarse-grained molecular dynamics (CGMD) and umbrella sampling. The results demonstrate that the process is spontaneous for the BP100 adsorbed on the AuNPs encapsulated with PEG. The PEG effect on the AuNP-BP100-PEG system works as a protection method or a ligand competition for BP100 transposition. However, it is observed that the BP100-PEG nanoparticle breaks up as reaching the aqueous phase. Then, BP100 migrates to the polar heads region of the negatively charged phospholipids. It is possible to evaluate the effects of nanocarriers on the LS model. Besides that it is suggested the feasibility of applying antimicrobial peptides carried on PEG capped AuNPs for possible treatments of lung diseases.

Transport of citrate and polymer coated gold nanoparticles (AuNPs) in porous media: Effect of surface property and Darcy velocity

With the release of nanoparticles (NPs) into the subsurface, it is imperative to better understand the fate and transport of NPs in porous media. Three types of stable AuNPs were used as model NPs to investigate the impact of surface coatings (type and coverage) and water velocity on the NP transport in a porous media (column studies). The NPs were electrostatic stabilized citrate AuNPs and sterically stabilized AuNPs with amphiphilic block co-polymer (PVA-COOH) in two particle/polymer ratios (weak vs. strong stabilization). The citrate AuNPs transport was sensitive to ionic changes in the mixing front of the plume, where destabilization occurred, and will therefore depend on the size/type of release. Blocking of deposition sites by aggregates was seen to facilitate transport, whereby a higher flow velocity (larger shadow zone) also resulted in better transport. The polymeric surface coating had great impact with steric repulsion as a main force contributing to the transport of NPs in the porous media. Sufficient polymer coating was crucial to obtain highly unfavorable attachment conditions (very low α) where the enhanced NP mobility was independent of the water velocity (comparable to solute tracer). Without sufficient steric stabilization, the transport and recovery was significantly reduced compared to the solute tracer, but increased with increasing water velocity. This highlights the importance of sufficient surface coating to achieve enhanced mobility, but also the increased risk of spreading to down-gradient receptors. For the (weakly) sterically stabilized NPs, the loss of polymer through ligand exchange with the porous media negates transport.

Anisotropic and heterogeneous dynamics in an aging colloidal gel.

We investigate the out-of-equilibrium dynamics of a colloidal gel obtained by quenching a suspension of soft polymer-coated gold nanoparticles close to and below its gelation point using X-ray Photon Correlation Spectroscopy (XPCS). A faster relaxation process emergent from the localized motions of the nanoparticles reveals a dynamically-arrested network at the nanoscale as a key signature of the gelation process. We find that the slower network dynamics is hyperdiffusive with a compressed exponential form, consistent with stress-driven relaxation processes. Specifically, we use direction-dependent correlation functions to characterize the anisotropy in dynamics. We show that the anisotropy is greater for the gel close to its gelation point than at lower temperatures, and the anisotropy decreases as the gel ages. We quantify the anisotropic dynamical heterogeneities emergent in such a stress-driven dynamical system using higher order intensity correlations, and demonstrate that the aging phenomenon contributes significantly to the properties evaluated by the fluctuations in the intensity correlations. Our results provide important insights into the structural origin of the emergent anisotropic and cooperative heterogeneous dynamics, and we discuss analogies with previous work on other soft disordered systems.

Functional design of pH-responsive folate-targeted polymer-coated gold nanoparticles for drug delivery and in vivo therapy in breast cancer.

BackgroundCurcumin has been widely used owing to its various medicinal properties including antitumor effects. However, its clinical application is limited by its instability, poor solubility and low bioavailability. Folic acid (FA)-functionalized nanoformulations may enhance the sustained release of an anticancer drug (curcumin) by tumor-specific targeting to improve therapeutic benefit. This study aims to design a nanoconjugate (NC) comprised of folate–curcumin-loaded gold–polyvinylpyrrolidone nanoparticles (FA–CurAu-PVP NPs) for targeted delivery in breast cancer model systems.MethodsWe developed curcumin-loaded FA-functionalized Au-PVP NCs by layer-by-layer assembly. The folic acid–curcumin Au-PVP NCs (FA–CurAu-PVP NCs) were characterized by ultraviolet–visible spectra, Fourier transform infrared spectroscopy, X-ray powder diffraction and thermogravimetric analysis. In vitro anticancer and antimigratory effects of NCs were examined by performing MTT and wound migration assays. The in vivo antitumor efficacy of NCs was investigated using a preclinical breast cancer orthotopic mouse model.ResultsCurcumin (40 µg/mL) was loaded along with conjugation of folate onto Au-PVP NPs to form FA–CurAu-PVP NCs. The size and charge of the NCs were increased gradually through layer-by-layer assembly and showed 80% release of curcumin at acidic pH. The NC did not show aggregation when incubated with human serum and mimicked an intrinsic peroxidase-like property in the presence of 3,3ʹ,5,5ʹ-tetramethylbenzidine substrate. The MTT data using these NCs showed efficient anticancer activity at lower doses in estrogen/progesterone receptor (ER/PR)-negative cells compared with ER/PR-positive cells. Furthermore, the NCs did not show cytotoxicity at the investigated concentration in human breast epithelial and mouse fibroblast cell lines. They showed inhibitory effects on cell migration and high antitumor efficacy in in vivo analysis.ConclusionThese results suggest that folate-based tumor targeting using CurAu-PVP NCs is a promising approach for tumor-specific therapy of breast cancer without harming normal cells.

Effect of polymer-coated gold nanoparticle stabilizers on drop coalescence

Polymer-coated gold nanoparticles (PGNPs) can be used as stabilizers in immiscible polymer blends, similar to block-copolymers (BCs). However, the PGNP gold cores increase the magnitude of the disjoining pressure (Π), i.e., the van der Waals interaction for unit area, in the film between the drops, favoring coalescence. This might explain the counterintuitive 70% drainage time (td) reduction for polymeric drops stabilized by PGNPs compared to those stabilized by BCs, as reported in recent flow-induced head-on collision experiments in extensional flow, despite PGNPs being more surface active. Knowledge of the mechanisms determining td is fundamental for designing effective PGNP compatibilizers. Here, we performed a parametric study of those experiments via boundary integral simulations, treating PGNPs as surfactants and utilizing for the first time a disjoining pressure expression which includes the effect of interfacial PGNPs (ΠPGNP). In particular, we varied the PGNP concentration and core size in ΠPGNP, the surface diffusivity (Ds) via the surface Peclet number, and the surface elasticity via the Marangoni number. Flow-induced coalescence was very sensitive to all three parameters. td was reduced up to 60% for touching 3 nm core diameter PGNPs, increasing significantly the coalescence probability for drop sizes <5 µm, but the soft coronas diminished this effect considerably. Thus, other causes, besides the enhanced Π, had to be simultaneously present to explain the dramatic experimental td reduction; the most likely is a Ds higher than its Stokes-Einstein relation estimate and the PGNP ligands being in a dry-brush regime, leading to entropic attraction between the drop interfaces.

Backscattered electron emission after proton impact on gold nanoparticles with and without polymer shell coating

This work aims at measuring experimentally proton induced secondary electron energy spectra after interaction with gold nano particles (GNPs) and polymer-coated GNPs. Backscattered electron energy spectra were collected over a 0 to 1000 eV energy range using a retarding field analyzer (RFA). This paper presents the spectra obtained for proton beam energies of 0.5 and 2 MeV and diameter 2.5 and 3.8 nm GNPs. The spectra were also measured for 3.8 nm GNPs after 5 and 10 MeV proton irradiations. GNPs were deposited on a 100 nm carbon film. Each experimental spectrum was compared with dedicated simulations based on existing numerical models used in the TRAX and Geant4 Monte Carlo codes.For 100 nm carbon target, good agreement between experimental, TRAX and Geant4 simulation results can be observed.For 3.8 nm GNPs, the TRAX simulations reproduce with good agreement the electron energy spectra produced after 0.5, 2, 5 and 10 MeV proton irradiations, while Geant4 spectra display a lower secondary electron yield at low energy (<600 eV) for all the studied energies. This underestimation can mostly be explained by the 790 eV threshold applied in the condensed history model used by Geant4 which impacts the secondary electron energy distribution. Results obtained for carbon and gold targets highlight the impact of the secondary electron production threshold for proton ionization process considered in condensed history models.The experimental results demonstrate that the single interaction approach used in TRAX is adapted to reproduce secondary electron emission from GNPs. On the other hand, the standard electron generation threshold implement in G4BetheBlochModel and G4BraggModel condensed-history models used in Geant4 is not adapted to reproduce low energy electron emission in gold targets.Finally, the results highlight that the GNP coating leads to a decrease of the electron yield and mostly affects low energy electrons (<500 eV) emitted from GNPs.

Rescued from the fate of neurological disorder.

Polymer-coated gold nanoparticles carrying the CRISPR components for knocking out, in the striatum of adult mice with fragile X syndrome, a gene implied in the syndrome’s pathophysiology rescue the mice from the exaggerated repetitive behaviours characteristic of the syndrome’s phenotype.

Distribution of polymer-coated gold nanoparticles in a 3D lung model and indication of apoptosis after repeated exposure.

The distribution and impact of aerosol-delivered gold nanoparticles (AuNPs) functionalized with a mixture of aminated-polyvinyl alcohol and amino-PEG ([polyvinyl alcohol/PEG]-NH2) upon repeated administration onto a 3D lung model were explored. AuNPs were aerosolized and uptake and epithelial translocation was assessed by inductively coupled plasma optical-emission spectroscopy, flow cytometry and electron microscopy. In addition, cytotoxicity, apoptosis and proinflammation were evaluated. Repeated AuNP aerosolization resulted in NP accumulation in macrophages and epithelial cells. Dendritic cells demonstrated substantial NP internalization after single administration which was reduced in later time points. No cytotoxicity or proinflammation was observed but after 96h significant apoptosis was induced by the polymer coating. These results indicate the importance of repeated exposures in addressing potential effects of NPs.

Switching of Macromolecular Ligand Display by Thermoresponsive Polymers Mediates Endocytosis of Multiconjugate Nanoparticles

Ligand-mediated targeting and internalization of plasma membrane receptors is central to cellular function. These types of receptors have accordingly been investigated as targets to facilitate entry of diagnostic and therapeutic constructs into cells. However, there remains a need to characterize how receptor targeting agents on nanoparticles interact at surface receptors and whether it is possible to control these interactions via exogenous stimuli. Here, we describe the switchable display of the iron-transporting protein, transferrin (Tf), at the surface of thermoresponsive polymer-coated gold nanoparticles and show that internalization of the coated nanoparticles into target cells changes across temperature ranges over which transferrin is expected to be sterically "hidden" by an extended polymer chain and then "revealed" by polymer chain collapse. The switching process is dependent on the numbers of transferrin molecules and thermoresponsive polymer chains attached and whether the assay temperature is above or below the transition temperatures of the responsive polymers at the nanoparticle surfaces. Significantly, however, the control of internalization is critically reliant on overall nanoparticle colloidal stability while the thermoresponsive component of the surface undergoes conformational change. The data show that the cell entry function of complex and large biomolecule ligands can be modulated by polymer-induced accessibility change but that a simple "hide and reveal" mechanism for ligand display following polymer chain collapse is insufficient to account for nanoparticle uptake and subsequent intracellular trafficking.

The functionalization of natural polymer-coated gold nanoparticles to carry bFGF to promote tissue regeneration.

Gold nanoparticles (AuNPs) enable the treatment and real-time monitoring of several diseases, providing an exciting and advantageous nanomedicine strategy. These NPs have therefore been adequately functionalized to enable them to carry growth factors (GF), namely basic fibroblastic (bF) GF, which play an essential role in different and important cellular processes including cellular proliferation, survival, migration and differentiation. The AuNPs were coated with natural polymers, chitosan and heparin, to enhance their physicochemical properties such as suspension stability. The polyelectrolyte coating was monitored using a quartz crystal microbalance with dissipation, size and zeta-potential analysis. The natural polymer-coated AuNPs have a spherical shape and a positive surface charge due to chitosan amino groups, enabling their biofunctionalization with monoclonal antibodies to target specific biomolecules. Additionally, cellular assays with the chondrocyte cell line ATDC5 show that the NPs are cytocompatible at relevant concentrations. As a proof of concept of their potential application in tissue regeneration, the natural polymer-coated AuNPs were further functionalized with an antibody to selectively bind the desired GF. The bFGF concentration reached in the NPs without compromising the cytocompatibility demonstrates the potential of this carrier for tissue regeneration.

Understanding the Cellular Uptake of pH-Responsive Zwitterionic Gold Nanoparticles: A Computer Simulation Study.

Surface functionalization of nanoparticles (NPs) with stealth polymers (e.g., hydrophilic and zwitterionic polymers) has become a common strategy to resist nonspecific protein adsorption recently. Understanding the role of surface decoration on NP-biomembrane interactions is of great significance to promote the application of NPs in biomedical fields. Herein, using coarse-grained molecular dynamics (CGMD) simulations, we investigate the interactions between stealth polymer-coated gold nanoparticles (AuNPs) and lipid membranes. The results show that AuNPs grafted with zwitterionic polymers can more easily approach the membrane surface than those coated with hydrophilic poly(ethylene glycol) (PEG), which can be explained by the weak dipole-dipole interaction between them. For zwitterionic AuNPs which can undergo pH-dependent charge conversion, different interaction modes which depend on the polymer protonation degree are found. When the protonation degree is low, the particles just adsorb on the membrane surface; at moderate protonation degrees, the particles can directly translocate across the lipid membrane through a transient hydrophilic pore formed on the membrane surface; the particles are fully wrapped by the curved lipid membrane at high protonation degrees, which may lead to endocytosis. Finally, the effect of polymer chain length on the cellular uptake of zwitterionic polymer-coated AuNPs is considered. The results demonstrate that longer polymer chain length will block the translocation of AuNPs across the lipid membrane when the protonation degree is not high; however, it can improve the transmembrane efficiency of AuNPs at high protonation degrees. We expect that these findings are of immediate interest to the design and synthesis of pH-responsive nanomaterials based on zwitterionic polymers and can prompt their further applications in the field of biomedicine.

Interaction of polymer-coated gold nanoparticles with cellobiose dehydrogenase: The role of surface charges

Studying the interaction of functional proteins such as enzymes and nanoparticles (NPs) includes the important topic of investigating any possible changes in stability and function of enzymes in nanostructured environments. The effects of NPs on the enzyme activity and stability are governed by their physical and chemical properties such as structure, shape, size, surface chemistry and their surface charges. In this study, the influence of negatively and positively charged AuNPs are investigated on the activity of immobilized Myriococcum thermophilum cellobiose dehydrogenase (MtCDH) and its electron transfer rate with graphite electrodes modified with positively and negatively AuNPs. The MtCDH modified graphite electrode premodified with positively charged AuNPs showed an alkaline shift in the pH of maximum activity from pH5.5 to 8. No change in the pH of maximum activity was observed when MtCDH graphite electrodes were premodified with negatively charged AuNPs. The results clearly demonstrated the effect of surface charge of AuNPs on the activity of the enzyme. The catalytic current density and the KMapp value for MtCDH graphite electrode premodified with positively charged AuNPs were enhanced with up to 66 and 8 times, respectively. Two spectroscopic assays were also performed in solution to investigate the influence of the presence of positively or negatively charged AuNPs on the activity of MtCDH in homogeneous solution. The results clearly demonstrated that not only the rate of the heterogeneous electron transfer between the immobilized MtCDH and the electrode but also the rate of the homogeneous electron transfer between soluble MtCDH and the acceptor was highly dependent on the type of surface charge of the AuNPs.

Affinity study on bovine serum albumin’s peptides to amphiphilic gold nanoparticles: A test of epitopes and non-epitopes

It is an inevitable event that nanoparticles (NPs) will encounter proteins/peptides in nano-medicine, so it has been significant to know their interaction mechanism before in vivo applications. Previously, a 105-amino-acid sequence had been reported as the binding site between bovine serum albumin (BSA) and amphiphilic polymer coated gold nanoparticles (AP-AuNPs) along with a mortise-tenon joint hypothesis. This article tested the affinity difference between two epitope peptide sequences such as: LGEYGFQNALIVR (S1), DAFLGSFLYEYSR (S2) and one non-epitope peptide sequence as: FDEHVKLVNELTEF (S3). With the photoluminescent amino acid residues, the fluorescence quenching method based on the nanometal surface energy transfer (NSET) principle was able to study the thermodynamics of the current binding system. The binding constants (Ka) were determined and followed the order as: Ka-S1>Ka-S2>>Ka-S3. Moreover, Hill constants indicated that cooperativity only presented in the interactions of AP-AuNP with either S1 or S2, but not for S3. Moreover, gel electrophoresis, surface plasmon resonance, atomic force microscopy and three dimensional fluorescence microscopy were all also used to comprehensively analyse the binding interaction mechanism. These results further provided useful information to better understand the mortise-tenon joint, which might find applications to nanofabrication and biomedicine.

Photothermal triggered protein release from an injectable polycaprolactone-based microspherical depot.

Upon exposure to visible light, controlled multiple dose protein release was demonstrated by using a microspherical depot composed of biodegradable poly(ε-caprolactone) (PCL), bovine serum albumin (BSA) or horseradish peroxidase (HRP) as model protein, polymer-coated gold nanoparticles as photothermal component, which can potentially reduce the number of invasive therapeutic injections.

Control of targeting ligand display by pH-responsive polymers on gold nanoparticles mediates selective entry into cancer cells.

Selective targeting of cells for intracellular delivery of therapeutics represents a major challenge for pharmaceutical intervention in disease. Here we show pH-triggered receptor-mediated endocytosis of nanoparticles via surface ligand exposure. Gold nanoparticles were decorated with two polymers: a 2 kDa PEG with a terminal folate targeting ligand, and a di-block copolymer including a pH-responsive and a hydrophilic block. At the normal serum pH of 7.4, the pH-responsive block (apparent pKa of 7.1) displayed a hydrophilic extended conformation, shielding the PEG-folate ligands, which inhibited cellular uptake of the nanoparticles. Under pH conditions resembling those of the extracellular matrix around solid tumours (pH 6.5), protonation of the pH-responsive polymer triggered a coil-to-globule polymer chain contraction, exposing folate residues on the PEG chains. In line with this, endocytosis of folate-decorated polymer-coated gold nanoparticles in cancer cells overexpressing folate receptor was significantly increased at pH 6.5, compared with pH 7.4. Thus, the tumour acidic environment and high folate receptor expression were effectively exploited to activate cell binding and endocytosis of these nanoparticles. These data provide proof-of-concept for strategies enabling extracellular pH stimuli to selectively enhance cellular uptake of drug delivery vectors and their associated therapeutic cargo.