Nanogel Surface Research Articles

Polysaccharide gel nanoparticles modified by the Layer-by-Layer technique for biomedical applications

Polysaccharide hydrogels have gained in recent years a considerable attention as one of the most promising materials for biomedical applications. Since they are of natural origin, with high biocompatibility and biodegradability, they are desirable materials in design of novel drug delivery devices. We prepared and characterized polysaccharide, alginate or pectin gel nanoparticles. They were prepared by the reverse microemulsions and physical crosslinking method by calcium (alginate) and zinc (pectin) ions. The average size of synthesized nanoparticles was ∼100nm and the batch concentration was 1010 particles/ml. Morphology of obtained gels nanoparticles were visualized by Cryo-Scanning Electron Microscopy. Then, surface of nanogels was modified by the Layer-by-Layer (LbL) technique using natural and synthetic polyelectrolytes. Encapsulation of fluorescent dyes (Rhodamine b and 5-aminofluorescein) in nanogels networks was performed. Cytotoxicity of non-modified and LbL modified nanoparticles was evaluated by the cellular viability quantification and cell death assessments using MTT and LDH biochemical tests, respectively.

Surfactant-free preparation of highly stable zwitterionic poly(amido amine) nanogels with minimal cytotoxicity

Narrowly dispersed zwitterionic poly(amido amine) (PAA) nanogels with a diameter of approximately 100nm were prepared by a high-yielding and surfactant-free, inverse nanoprecipitation of PAA polymers. The resulting, negatively charged, nanogels (PAA-NG1) were functionalized with N,N-dimethylethylenediamine via EDC/NHS coupling chemistry. This resulted in nanogels with a positive surface charge (PAA-NG2). Both types of nanogels were fluorescently labelled via isothiocyanate coupling. PAA-NG1 displays high colloidal stability both in PBS and Fetal Bovine Serum solution. Moreover, both nanogels exhibit a distinct zwitterionic swelling profile in response to pH changes. Cellular uptake of FITC-labelled nanogels with RAW 264.7, PC-3 and COS-7 cells was evaluated by fluorescence microscopy. These studies showed that nanogel surface charge greatly influences nanogel–cell interactions. The PAA polymer and PAA-NG1 showed minimal cell toxicity as was evaluated by MTT assays. The findings reported here demonstrate that PAA nanogels possess interesting properties for future studies in both drug delivery and imaging. Statement of significanceThe use of polymeric nanoparticles in biomedical applications such as drug delivery and imaging, shows great potential for medical applications. However, these nanoparticles are often not stable in biological environments. Zwitterionic polymers have shown excellent biocompatibility, but these materials are not easily degradable in biological environments. With the aim of developing a nanoparticle for drug delivery and imaging we synthesized a biomimetic and readily biodegradable zwitterionic polymer, which was incorporated into nanogels. These nanogels showed excellent stability in the presence of serum and minimal cytotoxicity, which was tested in three cell lines. Because of their negative surface charge and excellent serum stability, these nanogels are therefore promising carriers for drug delivery and molecular imaging.

Dual-temperature and pH responsive (ethylene glycol)-based nanogels via structural design

Dual-temperature and pH responsive (ethylene glycol)-based nanogels were synthesized. Both the core and the shell of the nanogels showed a lower critical solution temperature (LCST) and the LCST of the shell was strongly affected by the solution pH and salt concentration due to the presence of carboxylic acid groups at the nanogel surface.

Fabrication of nanogel core–silica shell and hollow silica nanoparticles via an interfacial sol–gel process triggered by transition-metal salt in inverse systems

Nanogel (hydrophilic polymer nanoparticles) core–silica shell nanoparticles were successfully fabricated via hydrolysis and condensation reaction of tetraethoxysilane (TEOS). Transition-metal tetrafluoroborate-containing nanogels were used as templates for fabrication in inverse systems (cyclohexane as continuous phase). Magnetic, hollow silica particles were subsequently formed by removing the polymer core and converting iron salts to iron oxides via heat treatment. We propose that the formation of the core–shell morphology is induced by the promoted precipitation of silica species at the surface of nanogels due to the interaction between silica species and transition-metal tetrafluoroborate. The influence of the synthesis parameters (type and amount of salts, pH of the nanogels, and amount of TEOS) on the particle morphology was systematically investigated. The pore properties and specific surface area of the hollow silica particles could be modified by the varying the amount of salt.

IRGD-coupled responsive fluorescent nanogel for targeted drug delivery

In this investigation, we have designed and synthesized a multifunctional nanogel for anti-tumor drug delivery. Thermo- and pH-responsive poly (N-isopropyl acrylamide-co-acrylic acid) nanogels (NGs) were synthesized by free radical precipitation polymerization. Positive charged chemotherapeutic drug doxorubicin (DOX) was introduced into the negatively charged swollen NGs by electrostatic adsorption at pH 7.4. Fluorescent bovine serum albumin (BSA) encapsulated gold nanoclusters (AuNCs) were conjugated onto the surface of NGs, followed by functionalization of tumor targeting peptide iRGD onto the BSA for tumor targeting. Interestingly, the DOX-encapsulated iRGD-decorated NGs maintain both thermo- and pH-responsive properties, which are favorable for achieving a controlled drug release in tumor tissues. Stable red fluorescent emission, derived from AuNCs, was used to detect and track the NGs in vitro. As expected, the iRGD motif mediated specific targeting to tumor and endothelial cells and enhanced cellular uptake of the NGs, as demonstrated by flow cytometry and confocal microscopy assays. In vitro cytotoxicity studies proved that the presence of iRGD enhanced the cytotoxic efficiency of DOX to the targeted cells. All together, our current study indicates that the NGs drug-carriers can deliver chemotherapeutic drug specifically to the tumor and endothelial cells with enhanced anti-tumor efficacy and controlled drug release.

Mixing and packing of binary hydrophobic silica aerogels

Particulate hydrophobic silica aerogel (Cabot Nanogel) is extremely porous, has the lowest density and lowest thermal conductivity of any solid, and is a much better insulator than air. Therefore it is advantageous to mix coarse and fine Nanogel particles to produce a uniform mixture that has a packing density (or bulk density) that is higher than that of either of the particles by themselves. A simple method to mix binary particles together without segregation is to add a small amount of liquid in a slowly rotating tumbler mixer. However, if water is used, the hydrophobicity of the Nanogel surface will repel the water and if an organic solvent is used, the solvent will simply enter the pores of the Nanogel. In this paper we use an ethanol water solution that has a lower surface tension than water, and a contact angle close to 90° so that it can wet the surface of the coarse particles without entering the pores. The mixtures so produced are very uniform without segregation and have packing densities very close to the predicted theoretical maximum for binary particles. Hydrophobic silica aerogel has a thermal conductivity lower than air. Binary particles can be uniformly mixed by adding a small amount of liquid in a tumbler mixer. We use an ethanol–water solution with a contact angle of 90 degrees to wet the coarse particles without entering the pores. The mixtures obtained have packing densities close to the predicted theoretical maximum. ► An ethanol-water solution was used to mix aerogel particles in a tumbler mixer. ► The solution needs to wet the coarse particles without entering the pores. ► The contact angle between the aerogel and solution has to be close to 90 degrees. ► The packing density increased with negligible segregation. ► The results agreed with the predicted theoretical maximum for binary particles.

Nanogel surface coatings for improved single-molecule imaging substrates

Surfaces that resist protein adsorption are important for many bioanalytical applications. Bovine serum albumin (BSA) coatings and multi-arm poly(ethylene glycol) (PEG) coatings display low levels of non-specific protein adsorption and have enabled highly quantitative single-molecule (SM) protein studies. Recently, a method was developed for coating a glass with PEG-BSA nanogels, a promising hybrid of these two low-background coatings. We characterized the nanogel coating to determine its suitability for SM protein experiments. SM adsorption counting revealed that nanogel-coated surfaces exhibit lower protein adsorption than covalently coupled BSA surfaces and monolayers of multi-arm PEG, so this surface displays one of the lowest degrees of protein adsorption yet observed. Additionally, the nanogel coating was resistant to DNA adsorption, underscoring the utility of the coating across a variety of SM experiments. The nanogel coating was found to be compatible with surfactants, whereas the BSA coating was not. Finally, applying the coating to a real-world study, we found that single ligand molecules could be tethered to this surface and detected with high sensitivity and specificity by a digital immunoassay. These results suggest that PEG-BSA nanogel coatings will be highly useful for the SM analysis of proteins.

Interpenetrating polymer network (IPN) nanogels based on gelatin and poly(acrylic acid) by inverse miniemulsion technique: Synthesis and characterization

Novel interpenetrating polymer network (IPN) nanogels composed of poly(acrylic acid) and gelatin were synthesised by one pot inverse miniemulsion (IME) technique. This is based on the concept of nanoreactor and cross-checked from template polymerization technique. Acrylic acid (AA) monomer stabilized around the gelatin macromolecules in each droplet was polymerized using ammonium persulfate (APS) and tetramethyl ethylene diamine (TEMED) in 1:5 molar ratio and cross-linked with N,N-methylene bisacrylamide (BIS) to form semi-IPN (sIPN) nanogels, which were sequentially cross-linked using glutaraldehyde (Glu) to form IPNs. Span 20, an FDA approved surfactant was employed for the formation of homopolymer, sIPN and IPN nanogels. Formation of stable gelatin–AA droplets were observed at 2% surfactant concentration. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) studies of purified nanogels showed small, spherical IPN nanogels with an average diameter of 255nm. In contrast, sIPN prepared using the same method gave nanogels of larger size. Fourier-transform infrared (FT-IR) spectroscopy, SEM, DLS, X-ray photoelectron spectroscopy (XPS) and zeta potential studies confirm the interpenetration of the two networks. Leaching of free PAA chains in sIPN upon dialysis against distilled water leads to porous nanogels. The non-uniform surface of IPN nanogels seen in transmission electron microscopy (TEM) images suggests the phase separation of two polymer networks. An increase of N/C ratio from 0.07 to 0.17 (from PAA gel to IPN) and O/C ratio from 0.22 to 0.37 (from gelatin gel to IPN) of the nanogels by XPS measurements showed that both polymer components at the nanogel surface are interpenetrated. These nanogels have tailoring properties in order to use them as high potential drug delivery vehicles for cancer targeting.

Nanogels prepared by self‐assembly of oppositely charged globular proteins

Ovalbumin and lysozyme are two main proteins in hen egg white with the isoelectric points of 4.8 and 11, respectively. Herein we report the manufacture of stable, narrowly distributed nanogels (hydrodynamic radius about 100 nm) using a novel and convenient method: ovalbumin and lysozyme solutions were mixed at pH 5.3, the mixture solution was adjusted to pH 10.3, then subsequently stirred and heated. The nanogels were characterized using a combination of techniques. The nanogels have spherical shape and core-shell structure. The core is mainly composed of lysozyme and the shell is mainly composed of ovalbumin. The proteins in the nanogels are in denatured states and they are bound by intermolecular hydrophobic interactions, hydrogen bonds, and disulfide bonds. The charges of the nanogels can be modulated by the pH of the medium. The electrostatic repulsion of ovalbumin molecules on the nanogel surface stabilizes the nanogels in aqueous solution. The formation mechanism of the nanogels is discussed.

Formation of Intra- and Interparticle Polyelectrolyte Complexes between Cationic Nanogel and Strong Polyanion

Polyelectrolyte complex formation of a strong polyanion, potassium poly(vinyl alcohol) sulfate (KPVS), with positively charged nanogels was studied at 25 degrees C in aqueous solutions with different KCl concentrations (C(s)) as a function of the polyion-nanogel mixing ratio based on moles of anions versus cations. Used as the gel sample was a polyampholytic nanogel consisting of lightly cross-linked terpolymer chains of N-isopropylacrylamide, acrylic acid, and 1-vinylimidazole; thus, the complexation was performed at pH 3 at which the imidazole groups are fully protonated to generate positive charges. Turbidimetric titration was employed to vary the mixing ratio. Also employed for studies of the resulting complexes at different stages of the titration were dynamic light scattering (DLS) and static light scattering (SLS) techniques. It was found from the titration as well as DLS and SLS that there is a critical mixing ratio (cmr) at which both the size and molar mass of the complexed gel particles abruptly increase. The value of the cmr at C(s) = 0 or 0.01 M (mol/L) was observed at approximately 1:1 mixing ratio of anions versus cations but at lower mixing ratios than the 1:1 ratio under conditions of C(s) = 0.05 and 0.1 M. At the mixing ratios less than the cmr, the molar mass of the complex agrees with that of one gel particle with the calculated amount of the bound KPVS ions, indicating the formation of an "intraparticle" KPVS-nanogel complex, by the aggregation of which an "interparticle" complex is formed at the cmr. During the process of the intraparticle complex formation, both the hydrodynamic radius by DLS and the radius gyration by SLS decreased with increasing mixing ratio, demonstrating the gel collapse due to the complexation. At C(s) = 0 or 0.01 M and under conditions where the amount of KPVS bindings was less than half of the nanogel cations, however, the decrease of the hydrodynamic radius was very small, while the radius gyration fell monotonically. These results were discussed in connection with a collapse of dangling chains attached to the nanogel surface by the binding of KPVS.