Ligand-installed PEGylated bionanosphere

The synthesis of poly(ethylene glycol)-b-poly(2-N,N-dimethylaminoethylmethacrylate) processing an acetal group at the PEG chain end (acetal-PEGPAMA) is reported. The obtained acetal-PEGPAMA block copolymer was found to reduce tetrachloroauric acid at room temperature to produce gold nanoparticles. The size of these nanoparticles was controllable in the range of 6 to 13 nm by changing the initial Au3+: polymer ratio. In addition to the reduction of tetrachloroauric acid, acetal-PEGPAMA bonds on the surface of the obtained gold nanoparticles to improve their dispersion stability in an aqueous medium even at a salt concentration as high as two. Biotinyl-PEGPAMA-anchored gold nanoparticles undergo specific aggregation in the presence of streptavidin thereby revealing their promising utility as colloidal sensing systems for use in biological systems. Biotin-PEGPAMA can also be utilised for the preparation of a functionally PEGylated quantum dot (QD). When CdCl2 and Na2S were mixed in aqueous media in the presence of the biotin-PEGPAMA, a CdS QD with an approximately 5 nm size was prepared. The polyamine segment was anchored onto the surface of the formed CdS nanoparticle, whereas the PEG segment was tethered onto the surface to form a hydrophilic palisade, thus improving the dispersion stability in aqueous media even under a high salt concentration condition. An effective fluorescent resonance energy transfer (FRET) was observed by the specific interaction of the biotin-PEGPAMA stabilised CdS QD with TexasRed-labelled streptavidin with the physiological ionic strength of 0.15 M. The extent of the energy transfer was in proportion to the concentration of the TexasRed-streptavidin. This FRET system using the PEGylated CdS QD coupled with fluorescent-labelled protein can be utilised as a highly sensitive bioanalytical system.     

自组装制备PEG接枝聚苯乙烯微球的粒径控制

用苯乙烯封端的聚乙二醇(St—PEG)大单体与苯乙烯(St)进行接枝共聚，将得到的双亲性接枝共聚物(PEG—g—PSt)逐步滴加到各种比例的甲醇／水的混合溶剂中，通过该聚合物在混合溶剂中的自组装，制得了PEG—g—PSt微球。用透射电子显微镜(TEM)和激光光散射(LLS)对微球的形态和粒径进行了表征。实验结果表明，改变接枝液组成、接枝液浓度、滴加速度以及混合溶剂组成等反应条件可有效地控制所得微球的粒径及其分布。     

Enhanced dispersity of gold nanoparticles modified by omega-carboxyl alkanethiols under the impact of poly(ethylene glycol)s

The physisorption of nonionic surfactant poly(ethylene glycol) (PEG) series and the chemisorption of carboxyl-terminated alkanethiols on surface of gold nanoparticles (AuNPs) were investigated. The physical adsorption of oligo(ethylene glycol) moieties introduced a tiny red shift of surface plasmon resonance (SPR) of AuNPs, indicating the formation of a protective layer of PEG molecules around gold surface. The subsequent chemisorption of omega-carboxyl alkanethiols was performed under the protection of PEG molecules, and the aggregation of metal nanoparticles did not appear by TEM observation. The successful adsorption of omega-carboxyl alkanethiol on gold surface was demonstrated according to FT-IR spectrum and the prior adsorbed PEG molecules could be washed out by centrifugation. Furthermore, the presence of nonionic surfactant even displayed a protective role in centrifugal process. The dispersity of modified AuNPs with peripheral functional groups was enhanced under the protection of PEG molecules as an important advantage in further biological applications.     

Microcapsules of PEGylated gold nanoparticles prepared by fluid-fluid interfacial assembly

Amphiphilic, PEGylated gold nanoparticles, of approximately 2 nm average core diameter, were synthesized by reduction of hydrogen tetrachloroaurate in the presence of the ligand (1-mercaptoundec-11-yl)tetra(ethylene glycol). These PEGylated gold nanoparticles were found to assemble cleanly at the oil-water interface. This self-assembly process gave a microencapsulated oil phase, water as the continuous phase, and a monolayer of gold nanoparticles at the oil-water interface. The capsules could be cross-linked from the organic phase by reaction of the chain-end hydroxyl groups of the PEG ligands with suitable electrophiles such as terephthaloyl chloride.     

Synthesis, stability, and cellular internalization of gold nanoparticles containing mixed peptide-poly(ethylene glycol) monolayers

Gold nanoparticles have shown great promise as therapeutics, therapeutic delivery vectors, and intracellular imaging agents. For many biomedical applications, selective cell and nuclear targeting are desirable, and these remain a significant practical challenge in the use of nanoparticles in vivo. This challenge is being addressed by the incorporation of cell-targeting peptides or antibodies onto the nanoparticle surface, modifications that frequently compromise nanoparticle stability in high ionic strength biological media. We describe herein the assembly of poly(ethylene glycol) (PEG) and mixed peptide/PEG monolayers on gold nanoparticle surfaces. The stability of the resulting bioconjugates in high ionic strength media was characterized as a function of nanoparticle size, PEG length, and monolayer composition. In total, three different thiol-modified PEGs (average molecular weight (MW), 900, 1500, and 5000 g mol-1), four particle diameters (10, 20, 30, and 60 nm), and two cell-targeting peptides were explored. We found that nanoparticle stability increased with increasing PEG length, decreasing nanoparticle diameter, and increasing PEG mole fraction. The order of assembly also played a role in nanoparticle stability. Mixed monolayers prepared via the sequential addition of PEG followed by peptide were more stable than particles prepared via simultaneous co-adsorption. Finally, the ability of nanoparticles modified with mixed PEG/RME (RME = receptor-mediated endocytosis) peptide monolayers to target the cytoplasm of HeLa cells was quantified using inductively coupled plasma optical emission spectrometry (ICP-OES). Although it was anticipated that the MW 5000 g mol-1 PEG would sterically block peptides from access to the cell membrane compared to the MW 900 PEG, nanoparticles modified with mixed peptide/PEG 5000 monolayers were internalized as efficiently as nanoparticles containing mixed peptide/PEG 900 monolayers. These studies can provide useful cues in the assembly of stable peptide/gold nanoparticle bioconjugates capable of being internalized into cells.     

Fabrication of Janus particles via a “photografting-from” method and gold photoreduction

Faster and simpler methods for the fabrication of Janus particles are of tremendous importance for a real implementation of these particles. By combining thiol-modified silica particles (SMPs) with the use of UV light, it is possible to rapidly fabricate Janus particles coated with polymer brushes and gold nanoparticles via photochemical emulsion-assisted route. From the silica particle surface, polymeric brushes of polyethylene(glycol), PEG, were grafted via a photografting-from method on one hemisphere by using the thiol groups as photoinitiator of the polymerization. The other hemisphere was coated with gold nanoparticles (AuNPs) generated in situ via photoreduction of chloroauric acid promoted by Norrish type I photoinitiator. PEG/AuNPs@SMPs coated with Au nanoparticles with average diameter of 12.7 or 22.5 nm were obtained by playing on the mass ratio between thiol-modified silica particles and gold precursor. The Janus PEG/AuNPs@SMPs were fully characterized by scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy and UV–Vis spectroscopy. This strategy merges the advantages of emulsion-based selective masking and UV-induced reactions, and it is proved to be a feasible and fast route (reactions are completed in dozens of minutes) for Janus particles fabrication.     

Dynamic light scattering and atomic force microscopy techniques for size determination of polyurethane nanoparticles

Nanoparticles have applications in various industrial fields principally in drug delivery. Nowadays, there are several processes for manufacturing colloidal polymeric systems and methods of preparation as well as of characterization. In this work, Dynamic Light Scattering and Atomic Force Microscopy techniques were used to characterize polyurethane nanoparticles. The nanoparticles were prepared by miniemulsion technique. The lipophilic monomers, isophorone diisocyanate (IPDI) and natural triol, were emulsified in water containing surfactant. In some formulations the poly(ethylene glycol) was used as co-monomer to obtain the hydrophilic and pegylated nanoparticles. Polyurethane nanoparticles observed by atomic force microscopy (AFM) were spherical with diameter around 209 nm for nanoparticles prepared without PEG. From AFM imaging two populations of nanoparticles were observed in the formulation prepared with PEG (218 and 127 nm) while dynamic light scattering (DLS) measurements showed a monodisperse size distribution around 250 nm of diameters for both formulations. The polydispersity index of the formulations and the experimental procedures could influence the particle size determination with these techniques.     

Thermally tunable catalytic and optical properties of gold-hydrogel nanocomposites

We have developed a very simple approach for preparing physically embedded gold cores in a temperature-responsive hydrogel polymer nanoparticle under fluorescent light irradiation. The complete encapsulation of the multiple gold core nanoparticles is confirmed by the catalytic reduction of 4-nitrophenol, whose reactivity is significantly retarded above the lower critical solution temperature (LSCT) due to the deswelled polymer structure; its increased hydrophobicity slows the access of hydrophilic reactants to the cores. Since these gold cores are physically embedded in the polymer nanoparticles, further growth of the cores is reliably achieved in situ under light irradiation. Interestingly, the resulting composite nanoparticles exhibit reversible solution color changes as well as absorption bands from the visible to near-IR regions below and above the LSCT.     

Synthesis of mesoporous silica monoliths with embedded nanoparticles

Mesostructured silica-nanoparticle monolithic composites have been synthesized by dispersing prefabricated nanoparticles of gold or zeolite (silicalite) in ethanolic reaction mixtures containing SiCl4 and a Pluronic triblock copolymer template. Whereas silicalite nanoparticles were used directly, surface functionalization of the gold nanoparticles with either primed silicate ions or a discrete 3-5-nm-thick silica shell was required to increase the interfacial compatibility with the hydrophilic poly(ethylene oxide) blocks. Under these conditions, the resulting monoliths consisted of distributed nanoparticles within an ordered mesostructured silica matrix. Removal of the polymer template by calcination produced corresponding mesoporous silica-nanoparticle replicas. The combination of the structure and the porosity of the silica framework with the crystal chemical properties of the embedded nanoparticles suggests that such composites should be useful as multifunctional materials.     

Increase in the vascular residence time of propranolol-loaded nanoparticles coated with heparin

Propranolol-HCI incorporated nanoparticles prepared with a blend of a polyester and a polycationic polymer and coated or not with a low molecular weight heparin by electrostatic interactions were prepared by emulsification followed by solvent evaporation. The mean diameter was 388 and 357 nm for coated and uncoated nanoparticles, respectively, and the entrapment efficiency ranged from 20 to 32%. Coated nanoparticles were negatively-charged, whereas uncoated nanoparticles displayed a positive zeta potential (+30 mV). After intravenous administration to rabbits of propranolol-HCI solution and propranolol-loaded nanoparticles coated or not with heparin, pharmacokinetic data revealed that coated nanoparticles exhibited a prolonged blood residence time. It can be concluded that the hydrophilic layer of heparin at the surface of nanoparticles conferred stealth properties which probably reduce the phagocytosis process and avoid immediate uptake by the mononuclear phagocytic system.     

Spatio-selective surface modification of glass assisted by laser-induced deposition of gold nanoparticles

Using pulsed laser irradiation (532 nm), dodecanethiol-capped gold nanoparticles (DT-Au) were deposited on the laser-irradiated region of a hydrophobic glass substrate modified with dimethyloctadecylchlorosilane (DMOS). After removal of deposited DT-Au, the laser-deposited region on the substrate was hydrophilic, as verified by static water contact angles. X-ray photoelectron spectroscopy suggested that the naked glass surface was not exposed at the hydrophilic region. Immersion of the substrate into gold nanorod (NR) solution selectively immobilized NRs on the hydrophilic surface via electrostatic interactions, indicating that the hydrophilic region was an anionic surface. From these results, it is expected that some immobilized DMOS groups on the laser-irradiated region of the substrate were oxidized during DT-Au deposition and fragmentation of the deposited DT-Au.     

Surface-modified superparamagnetic nanoparticles for drug delivery: preparation, characterization, and cytotoxicity studies

Superparamagnetic iron oxide nanoparticles have been used for many years as magnetic resonance imaging (MRI) contrast agents or in drug delivery applications. In this study, a novel approach to prepare magnetic polymeric nanoparticles with magnetic core and polymeric shell using inverse microemulsion polymerization process is reported. Poly(ethyleneglycol) (PEG)-modified superparamagnetic iron oxide nanoparticles with specific shape and size have been prepared inside the aqueous cores of AOT/n-Hexane reverse micelles and characterized by various physicochemical means such as transmission electron microscopy (TEM), infrared spectroscopy, atomic force microscopy (AFM), vibrating sample magnetometry (VSM), and ultraviolet/visible spectroscopy. The inverse microemulsion polymerization of a polymerizable derivative of PEG and a cross-linking agent resulted in a stable hydrophilic polymeric shell of the nanoparticles. The results taken together from TEM and AFM studies showed that the particles are spherical in shape with core-shell structure. The average size of the PEG-modified nanoparticles was found to be around 40-50 nm with narrow size distribution. The magnetic measurement studies revealed the superparamagnetic behavior of the nanoparticles with saturation magnetization values between 45-50 electromagnetic units per gram. The cytotoxicity profile of the nanoparticles on human dermal fibroblasts as measured by standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the particles are nontoxic and may be useful for various in vivo and in vitro biomedical applications.     

Enhanced bio-compatibility of ferrofluids of self-assembled superparamagnetic iron oxide-silica core-shell nanoparticles

Self-assembled magnetic colloidal suspensions are sought after by material scientists owing to its huge application potential. The biomedical applications of colloidal nanoparticles necessitate that they are biocompatible, non-interacting, monodispersed and hence the synthesis of such nanostructures has great relevance in the realm of nanoscience. Silica-coated superparamagnetic iron oxide nanoparticles based ferrofluids were prepared using polyethylene glycol as carrier fluid by employing a controlled co-precipitation technique followed by a modified sol-gel synthesis. A plausible mechanism for the formation of stable suspension of SiO2-coated Iron Oxide nanoparticles with a size of about 9 nm dispersed in polyethylene glycol (PEG) is proposed. Core-shell nature of the resultant SiO2-Iron Oxide nanocomposite was verified using transmission electron microscopy. Fourier transform-infrared spectroscopy studies were carried out to understand the structure and nature of chemical bonds. The result suggests that Iron Oxide exist in an isolated state inside silica matrix. Moreover, the presence of silanol bonds establishes the hydrophilic nature of silica shell confirming the formation of stable ferrofluid with PEG as carrier fluid. The magnetic characterization reveals the superparamagnetic behavior of the nanoparticles with a rather narrow distribution of blocking temperatures. These properties are not seen in ferrofluids prepared from Iron Oxide nanoparticles without SiO2 coating. The latter suggests the successful tuning of the inter-particle interactions preventing agglomeration of nanoparticles. Cytotoxicity studies on citric acid coated water based ferrofluid and silica-coated PEG-based ferrofluid were evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium chloride assay and it shows an enhanced compatibility for silica modified nanoparticles.     

Nanoparticle Regrowth Enhances Photoacoustic Signals of Semiconducting Macromolecular Probe for In Vivo Imaging

Smart molecular probes that emit deep‐tissue penetrating photoacoustic (PA) signals responsive to the target of interest are imperative to understand disease pathology and develop innovative therapeutics. This study reports a self‐assembly approach to develop semiconducting macromolecular activatable probe for in vivo imaging of reactive oxygen species (ROS). This probe comprises a near‐infrared absorbing phthalocyanine core and four poly(ethylene glycol) (PEG) arms linked by ROS‐responsive self‐immolative segments. Such an amphiphilic macromolecular structure allows it to undergo an ROS‐specific cleavage process to release hydrophilic PEG and enhance the hydrophobicity of the nanosystem. Consequently, the residual phthalocyanine component self‐assembles and regrows into large nanoparticles, leading to ROS‐enhanced PA signals. The small size of the intact macromolecular probe is beneficial to penetrate into the tumor tissue of living mice, while the ROS‐activated regrowth of nanoparticles prolongs the retention along with enhanced PA signals, permitting imaging of ROS during chemotherapy. This study thus capitalizes on stimuli‐controlled self‐assembly of macromolecules in conjunction with enhanced heat transfer in large nanoparticles for the development of smart molecular probes for PA imaging.     

Enhanced x-ray irradiation-induced cancer cell damage by gold nanoparticles treated by a new synthesis method of polyethylene glycol modification

We explored a very interesting gold nanoparticle system-pegylated gold in colloidal solution-and analyzed its uptake by mice colorectal adenocarcinoma CT26 tumor cells and the impact on the cell's response to x-ray irradiation. We found that exposure to polyethylene glycol (PEG) modified ('pegylated') 4.7 ± 2.6?nm gold nanoparticles synthesized by a novel synchrotron-based method enhances the response of CT26 cells to x-ray irradiation. Transmission electron microscopy (TEM) and confocal microscopy revealed that substantial amounts of such nanoparticles are taken up and absorbed by the cells and this conclusion is supported by quantitative induced coupled plasma (ICP) results. Standard tests indicated that the internalized particles are highly biocompatible but strongly enhance the cell damage induced by x-ray irradiation. Synchrotron radiation Fourier transform infrared (SR-FTIR) spectromicroscopy analyzed the chemical aspects of this phenomenon: the appearance of C = O stretching bond spectral features could be used as a marker for cell damage and confirmed the enhancement of the radiation-induced toxicity for cells.     

Synthesis of magnetite/amphiphilic polymer composite nanoparticles as potential theragnostic agents

This study describes the synthesis of magnetite/amphiphilic polymer composite nanoparticles that can be potentially used simultaneously for cancer diagnosis and therapy. The synthesis method was a one-shot process wherein magnetite nanoparticles were mixed with core-crosslinked amphiphilic polymer (CCAP) nanoparticles, prepared using a copolymer of a urethane acrylate nonionomer (UAN) and a urethane acrylate anionomer (UAA). The CCAP nanoparticles had a hydrophobic core and a hydrophilic exterior with both PEG segments and carboxylic acid groups, wherein the magnetite nanoparticles were coordinated and stabilized. According to DLS data, the ratio of UAN to UAA and the ratio of magnetite to polymer are keys to controlling the size and thus, the stability of the composite nanoparticles. The magnetic measurement indicated that the composite nanoparticles had superparamagnetic properties and high saturation magnetization. The preliminary magnetic resonance imaging showed that the particles produced an enhanced image even when their concentration was as low as 80 microg/ml.     

X-ray computed tomography imaging of a tumor with high sensitivity using gold nanoparticles conjugated to a cancer-specific antibody via polyethylene glycol chains on their surface

Contrast agents are often used to enhance the contrast of X-ray computed tomography (CT) imaging of tumors to improve diagnostic accuracy. However, because the iodine-based contrast agents currently used in hospitals are of low molecular weight, the agent is rapidly excreted from the kidney or moves to extravascular tissues through the capillary vessels, depending on its concentration gradient. This leads to nonspecific enhancement of contrast images for tissues. Here, we created gold (Au) nanoparticles as a new contrast agent to specifically image tumors with CT using an enhanced permeability and retention (EPR) effect. Au has a higher X-ray absorption coefficient than does iodine. Au nanoparticles were supported with polyethylene glycol (PEG) chains on their surface to increase the blood retention and were conjugated with a cancer-specific antibody via terminal PEG chains. The developed Au nanoparticles were injected into tumor-bearing mice, and the distribution of Au was examined with CT imaging, transmission electron microscopy, and elemental analysis using inductively coupled plasma optical emission spectrometry. The results show that specific localization of the developed Au nanoparticles in the tumor is affected by a slight difference in particle size and enhanced by the conjugation of a specific antibody against the tumor.     

The effect of capping agents on the structural and magnetic properties of cobalt ferrite nanoparticles

Microwave-assisted co-precipitation method was adopted to analyze the effect of polyethylene glycol (PEG) and urea concentrations on the properties of cobalt ferrite nanoparticles (NPs). The average crystallite size of single phase cubic spinel cobalt ferrite NPs was controlled within 10–14 nm with the effect of PEG, urea and the combination of them. The transmission electron micrographs revealed that the morphology of cobalt ferrites was not significantly influenced by the different concentration of capping agents but almost uniform morphology with nearly narrow size distribution was obtained. The interaction of PEG and urea molecules on the surface of nanoparticles was mediated through –OH hydroxyl group affected the crystal growth rate. The possible interaction mechanism was proposed with the help of IR vibrational spectra. All the samples exhibited ferromagnetism at room temperature and it was found that the capping agents showed an effect on the magnetic properties. The maximum saturation magnetization of 58 emu/g was achieved when the urea of 60 mg was used and the maximum coercivity of 311 Oe was attained when the mixture of PEG (40 mg) and urea (20 mg) were used. Ultrafine and hydrophilic cobalt ferrite NPs that showed appreciable magnetic properties obtained in the present experimental procedure would be of great interest in various biomedical applications.     

Freeze-Drying of Composite Core-Shell Nanoparticles

ABSTRACT

The effects of four sugars (glucose, saccharose, maltose, trehalose) and one surfactant (Poloxamer 188), on the freeze-drying of poly(isobutylcyanoacrylate) (PIBCA), poly(ε-caprolactone)-poly(ethylene glycol) (PCL-PEG), and novel core (mainly PIBCA)-shell (principally PEG) composite nanoparticles (CNP) obtained by co-precipitation were investigated. The efficiency of the additives against the adverse effect of freeze-drying on the redispersibility of the nanoparticles was evaluated, based on the visual appearance of the nanoparticle suspensions (Tyndall effect and aggregation), and on the determination of the mean diameter ratio of the nanoparticles before and after freeze-drying. The results indicated that the addition of both sugars and surfactant was essential for the good redispersion of freeze-dried nanoparticles displaying hydrophobic (PIBCA) or hydrophilic (PCL-PEG and CNP) surfaces.     

Freeze-drying of composite core-shell nanoparticles

The effects of four sugars (glucose, saccharose, maltose, trehalose) and one surfactant (Poloxamer 188), on the freeze-drying of poly(isobutylcyanoacrylate) (PIBCA), poly(ε-caprolactone)-poly(ethylene glycol) (PCL-PEG), and novel core (mainly PIBCA)-shell (principally PEG) composite nanoparticles (CNP) obtained by co-precipitation were investigated. The efficiency of the additives against the adverse effect of freeze-drying on the redispersibility of the nanoparticles was evaluated, based on the visual appearance of the nanoparticle suspensions (Tyndall effect and aggregation), and on the determination of the mean diameter ratio of the nanoparticles before and after freeze-drying. The results indicated that the addition of both sugars and surfactant was essential for the good redispersion of freeze-dried nanoparticles displaying hydrophobic (PIBCA) or hydrophilic (PCL-PEG and CNP) surfaces.