Venkateshwarlu Gopishetty

Specific Biochemical-to-Optical Signal Transduction by Responsive Thin Hydrogel Films Loaded with Noble Metal Nanoparticles

2010 WILEY-VCH Verlag Gmb This Communication concerns the combination of three distinct phenomena—a biocatalytic process, localized surface plasmon resonance (LSPR) effects in noble metal nanoparticles, and the swelling–shrinking transition in a stimuli-responsive hydrogel— with the aim to create a novel sensing platform for two important applications: analysis of biomolecules (biosensors) and probing (monitoring) of local properties of biomaterials. The above combination allowed us to realize an efficient biochemicalto-optical signal transduction scheme, possessing high specificity and diminishing the impact of nonspecific interactions. LSPR effects in noble metal nanoparticles are observed through a color by the naked eye or in a transmission visible spectrum that reveals characteristic absorbance bands. The LSPR absorption is much more pronounced compared to organic dyes. Furthermore, LSPR spectra are sensitive to the immediate particle environment. In particular, changes in the refractive index of the environment in the close vicinity to the particle surface or in the interparticle plasmon coupling result in the alternation of the spectrum (i.e., changes in position, width, and intensity of the extinction bands). The sensitivity of LSPR spectra to the immediate environment has been recently explored for bioanalytical applications. In these studies, biomolecules (DNA or antibodies) were immobilized onto noble metal nanoparticles. Then, the biorecognition events were detected through changes in the chemical composition occurring on the surfaces of colloidal nanoparticles or supported nanoparticle arrays (nanoislands). In some studies, the hybridization events were detected through the reversible aggregation of dispersed noble metal nanoparticles capped with the complementary oligonucleotides; the aggregation was accompanied by plasmon coupling among the particles and led to noticeable changes in the color of the dispersion. One of the most important advantages of LSPR spectroscopy is the high stability and biocompatibility of the noble metal nanoparticles compared to organic dyes and quantum dots. Alternatively, the changes in LSPR spectra of the nanoparticles can be tuned by a stimuli-responsive polymeric material. For example, swelling–shrinking of a polymer network (gel) or a monolayer of polymer chains tethered to a transparent substrate may lead to changes in the local refractive index of gold or silver nanoparticles entrapped in the polymeric material or/and in the average interparticle distance. In previous studies, the swelling transitions in responsive polymeric materials were initiated by changes in the pH and temperature of aqueous media. Hence, the transformations of chemical and physical signals into the optical effect were used for analytical applications. In this work, we extend the analytical potential of plasmonic sensing devices based on the combination of noble metal nanoparticles and stimuli-responsive polymeric materials by coupling them with highly specific enzymatic reactions. To date, numerous sensing platforms have been demonstrated on the basis of biocatalytic processes. Many of them were realized for measuring glucose levels in blood by using catalytic oxidation of glucose in the presence of glucose oxidase (GOx) and detecting the pH changes produced in the course of this enzymatic reaction. Here, we explore this approach in a novel plasmonic sensing platform. One of the major issues in biosensors is that, being applied for analysis of biological fluids, such as blood, they produce a false response caused by fouling of the sensing elements with proteins. We overcome this problem in the proposed material. Besides biosensing, another important application of the developed approach is in situ probing of materials, where the changes in optical properties are used to extract the information about local changes in the material structure or properties (e.g., the degree of swelling). The latter is especially important for biomaterials used in nonequilibrium conditions. For example, biodegradable implants or scaffolds for tissue engineering may experience local changes in the pH or concentrations of various ions. In particular, this may happen when pH changes induced by products of degradation (e.g., lactic acid) are too rapid to be equilibrated by physiological mechanisms. Measuring changes in the local structure and properties of responsive materials coupled with LSPR effects provides valuable information for understanding their dynamic behavior and can also be used to remotely and noninvasively monitor the material’s state. The plasmonic sensing platform, depicted in Figure 1, consists of a transparent glass support decorated with silver nanoislands ca. 12–14 nm thick (3), a 20–25 nm, pH-responsive, hydrogel thin film (1), and silver nanoparticles (2) encapsulated in the film. The film thickness is chosen in such a way that the Ag nanoparticles are confined in the immediate vicinity to the nanoislands, thus enabling their efficient plasmon coupling. The particles are completely encapsulated by the hydrogel in the sense that they are

Biocompatible stimuli-responsive hydrogel porous membranes via phase separation of a polyvinyl alcohol and Na-alginate intermolecular complex

Ion cross-linked porous alginate thin films were fabricated from mixtures of sodium alginate and polyvinyl alcohol (PVA) in an aqueous solution. A spinodal decomposition mechanism in a low immiscibility limit brings about the formation of phase separated spin-cast thin films that are characterized with a low size distribution of PVA phases. Rinsing of the films in calcium chloride solutions yields porous hydrogel films – membranes on solid substrates. The porous membranes are a pH-sensitive material whose pore diameter can be tuned by changes in pH. The membranes are mechanically robust and can be transferred onto the surface of porous substrates.

Wound-healing with mechanically robust and biodegradable hydrogel fibers loaded with silver nanoparticles.

The objective of this study is to provide a novel synthetic approach for the manufacture of wound-healing materials using covalently cross-linked alginate fibers loaded with silver nanoparticles. Alginate fibers are prepared by wet-spinning in a CaCl(2) precipitation bath. Using this same approach, calcium cross-links in alginate fibers are replaced by chemical cross-links that involve hydroxyl groups for subsequent cross-linking by glutaraldehyde. The cross-linked fibers become highly swollen in aqueous solution due to the presence of carboxyl functional groups, and retain their mechanical stability in physiological fluids owing to the stabilized network of covalent bonds. Alginate fibers can then be loaded with silver ions via the ion-exchange reaction. Silver ions are reduced to yield 11 nm silver nanoparticles incorporated in the polymer gel. This method provides a convenient platform to incorporate silver nanoparticles into alginate fibers in controlled concentrations while retaining the mechanical and swelling properties of the alginate fibers. Our study suggests that the silver nanoparticles loaded fibers may be easily applied in a wound healing paradigm and promote the repair process though the promotion of fibroblast migration to the wound area, reduction of the inflammatory phase, and the increased epidermal thickness in the repaired wound area, thereby improving the overall quality and speed of healing.

Highly Porous 3D Fibrous Nanostructured Bioplolymer Films with Stimuli-Responsive Porosity via Phase Separation in Polymer Blend

The article describes a novel polymer blend system that yields thin films with unique porous nanoscale morphologies and environmentally responsive properties. The blend consists of sodium alginate and amine end-terminated PEG, which undergoes phase separation during film deposition. The blend films can be readily converted into highly porous membranes using facile treatment with a solution containing divalent ions. The resulting membranes are primarily comprised of alginate hydrogel, whereas the PEG phase is removed from the films during exposure to the saline solution, yielding nanometer-sized pores. The alginate gel phase forms a three-dimensional nanostructure which can be best described as a filament or fibrous network. Because such network geometry is untypical of polymer blends in thin films, possible reasons for the observed phase morphology are discussed. Because of ionizable carboxyl groups, the hydrogel membranes demonstrate responsive behavior, in particular a drastic change in their porosity between a highly porous state and a state with completely closed pores in response to changes in the solution pH. The pore-size tunability can be explored in multiple applications where the regulation of materials permeability is needed.