Probing the Ultimate Limits of Plasmonic Enhancement Ciracì, C.; Hill, R. T.; Mock, J. J. ...
Science (American Association for the Advancement of Science),
08/2012, Letnik:
337, Številka:
6098
Journal Article
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Metals support surface plasmons at optical wavelengths and have the ability to localize light to subwavelength regions. The field enhancements that occur in these regions set the ultimate limitations ...on a wide range of nonlinear and quantum optical phenomena. We found that the dominant limiting factor is not the resistive loss of the metal, but rather the intrinsic nonlocality of its dielectric response. A semiclassical model of the electronic response of a metal places strict bounds on the ultimate field enhancement. To demonstrate the accuracy of this model, we studied optical scattering from gold nanoparticles spaced a few angstroms from a gold film. The bounds derived from the models and experiments impose limitations on all nanophotonic systems.
The in‐situ synthesis of oligo(ethylene glycol)‐functionalized polymer brushes from a self‐assembled monolayer of an alkanethiol on gold that presents a tethered initiator by surface‐initiated atom ...transfer radical polymerization is reported. These polymer brushes exhibit no detectable adsorption of proteins, and are cell‐resistant for up to a month under typical cell culture conditions. The synthesis method is compatible with a range of patterning techniques from the nano‐ to the microscale, and enables the patterning of cells in a biologically relevant milieu over extended periods of time. Images of the brushes are shown on the inside front cover.
Surfaces modified with stimuli‐responsive polymers (SRPs) dynamically alter their physico‐chemical properties in response to changes in their environmental conditions. The triggered control of ...interfacial properties provided by immobilized SRPs at the solid–water interface has application in the design of biomaterials, regenerable biosensors, and microfluidic bioanalytical devices. In this article, we briefly summarize recent research in this area, followed by two recent examples of research from our laboratory on stimuli‐responsive surfaces. First, we present a new assay to quantify the phase transition behavior of SRPs at the solid–water interface. This assay, which is based on the distance‐dependent colorimetric properties of gold nanoparticles, provides a technically simple and convenient method to determine the effect of different variables on the lower critical solution temperature (LCST) behavior of SRPs at the solid–water interface. Second, we show that stimuli‐responsive surfaces can be created by the immobilization of an elastin‐like polypeptide (ELP), a thermally responsive biopolymer, on a glass surface. We exploit the phase transition of the ELP at a surface to reversibly address an ELP fusion protein to a surface. This method, which we term thermodynamically reversible addressing of proteins (TRAP), enables the reversible, spatio‐temporal modulation of protein binding at the solid‐liquid interface, and will enable the realization of new bioanalytical applications.
“Smart” surfaces that modulate their physico‐chemical properties in response to environmental triggers can be fabricated by functionalization of a surface with stimuli‐responsive polymers (SRPs). This article summarizes different approaches to the fabrication of “smart” surfaces and their applications. Recent results that demonstrate reversible micropatterning of proteins using a smart biopolymer as well as a simple, colorimetric assay to characterize the phase transition behavior of SRPs at the solid–water interface are highlighted.
This paper describes the in‐situ synthesis of an oligo(ethylene glycol)‐functionalized polymer brush in which the oligo(ethylene glycol) chains are presented as side‐chains from a methacrylate ...backbone that is anchored to the surface. These polymer “bottlebrushes” have been synthesized by surface‐initiated atom transfer radical polymerization (SI‐ATRP) of oligo(ethylene glycol) methyl methacrylate (OEGMA) from a mixed self‐assembled monolayer (SAM) of an ATRP initiator‐functionalized alkanethiol and a diluent, methyl‐terminated thiol. The systematic control of the ATRP initiator surface density afforded by the mixed SAM on gold and the polymerization time enables the polymer chain length and surface density to be independently controlled. Surface plasmon resonance (SPR) spectroscopy of fibronectin (Fn) adsorption on poly(OEGMA) grown from the surface of the mixed SAMs on gold shows that above a threshold solution molar ratio of the ATRP‐initiator thiol to methyl‐terminated thiol of 0.2, and a dry film thickness of ∼ 4 nm, Fn adsorption on the surface‐initiated poly(OEGMA) coatings was below the detection limit of SPR. The relatively low surface density of the ATRP initiator required to confer protein resistance to the surface suggests that SI‐ATRP may be a viable strategy to create protein resistant polymer brushes on real‐world materials.
The in‐situ synthesis of protein‐resistant polymer films by surface‐initiated ATRP of oligo(ethylene glycol) methyl methacrylate from mixed SAMs of initiator‐functionalized alkanethiol/ diluent thiol is described (see Figure). Above a threshold solution molar ratio of the initiator thiol to diluent thiol of 0.2, and a dry‐film thickness of ∼4 nm, fibronectin adsorption on the polymer coatings was below 1 ng cm–2.
Peptide drugs are an exciting class of pharmaceuticals for the treatment of a variety of diseases; however, their short half-life dictates multiple and frequent injections causing undesirable side ...effects. Herein, we describe a novel peptide delivery system that seeks to combine the attractive features of prolonged circulation time with a prolonged release formulation. This system consists of glucagon-like peptide-1, a type-2 diabetes drug fused to a thermally responsive, elastin-like-polypeptide (ELP) that undergoes a soluble–insoluble phase transition between room temperature and body temperature, thereby forming an injectable depot. We synthesized a set of GLP-1-ELP fusions and verified their proteolytic stability and potency in vitro. Significantly, a single injection of depot forming GLP-1-ELP fusions reduced blood glucose levels in mice for up to 5days, 120 times longer than an injection of the native peptide. These findings demonstrate the unique advantages of using ELPs to release peptide-ELP fusions from a depot combined with enhanced systemic circulation to create a tunable peptide delivery system.
A fusion of glucagon-like peptide-1 and elastin-like polypeptide is able to reduce blood glucose for over 5days after a single injection by forming an extended release subcutaneous depot and prolonging peptide circulation time. Display omitted
Post-traumatic arthritis (PTA) is a rapidly progressive form of arthritis that develops due to joint injury, including articular fracture. Current treatments are limited to surgical restoration and ...stabilization of the joint; however, evidence suggests that PTA progression is mediated by the upregulation of pro-inflammatory cytokines, such as interleukin-1 (IL-1) or tumor necrosis factor-α (TNF-α). Although these cytokines provide potential therapeutic targets for PTA, intra-articular injections of anti-cytokine therapies have proven difficult due to rapid clearance from the joint space. In this study, we examined the ability of a cross-linked elastin-like polypeptide (xELP) drug depot to provide sustained intra-articular delivery of IL-1 and TNF-α inhibitors as a beneficial therapy. Mice sustained a closed intra-articular tibial plateau fracture; treatment groups received a single intra-articular injection of drug encapsulated in xELP. Arthritic changes were assessed 4 and 8 weeks after fracture. Inhibition of IL-1 significantly reduced the severity of cartilage degeneration and synovitis. Inhibition of TNF-α alone or with IL-1 led to deleterious effects in bone morphology, articular cartilage degeneration, and synovitis. These findings suggest that IL-1 plays a critical role in the pathogenesis of PTA following articular fracture, and sustained intra-articular cytokine inhibition may provide a therapeutic approach for reducing or preventing joint degeneration following trauma.
There is great interest in identifying a glucagon-like peptide-1 (GLP-1)-based combination therapy that will more effectively promote weight loss in patients with type 2 diabetes. Fibroblast growth ...factor 21 (FGF21) is a compelling yet previously unexplored drug candidate to combine with GLP-1 due to its thermogenic and insulin-sensitizing effects. Here, we describe the development of a biologic that fuses GLP-1 to FGF21 with an elastin-like polypeptide linker that acts as a sustained release module with zero-order drug release. We show that once-weekly dual-agonist treatment of diabetic mice results in potent weight-reducing effects and enhanced glycemic control that are not observed with either agonist alone. Furthermore, the dual-agonist formulation has superior efficacy compared to a GLP-1/FGF21 mixture, demonstrating the utility of combining two structurally distinct peptides into one multifunctional molecule. We anticipate that these results will spur further investigation into GLP-1/FGF21 multiagonism for the treatment of metabolic disease.
The change in optical properties of colloidal gold upon aggregation has been used to develop an experimentally convenient colorimetric method to study the interfacial phase transition of an ...elastin-like polypeptide (ELP), a thermally responsive biopolymer. Gold nanoparticles, functionalized with a self-assembled monolayer (SAM) of mercaptoundecanoic acid onto which an ELP was adsorbed, exhibit a characteristic red color due to the surface plasmon resonance (SPR) of individual colloids. Raising the solution temperature from 10 degrees C to 40 degrees C thermally triggered the hydrophilic-to-hydrophobic phase transition of the adsorbed ELP resulting in formation of large aggregates due to interparticle hydrophobic interaction. Formation of large aggregates caused a change in color of the colloidal suspension from red to violet due to coupling of surface plasmons in aggregated colloids. The surface phase transition of the ELP was reversible, as seen from the reversible change in color upon cooling the suspension to 10 degrees C. The formation of colloidal aggregates due to the interfacial phase transition of adsorbed ELP was independently verified by dynamic light scattering of ELP-modified gold colloids as a function of temperature. Colloidal SPR provides a simple and convenient colorimetric method to study the influence of the solution environment, interfacial properties, and grafting method on the transition properties of ELPs and other environmentally responsive polymers at the solid-water interface.
We use optical darkfield micro-spectroscopy to characterize the plasmon resonance of individual silver nanoparticles in the presence of a substrate. The optical system permits multiple individual ...nanoparticles to be identified visually for simultaneous spectroscopic study. For silver particles bound to a silanated glass substrate, we observe changes in the Plasmon resonance due to induced variations in the local refractive index. The shifts in the plasmon resonance are investigated using a simple analytical theory in which the contributions from the substrate and environment are weighted with distance from the nanoparticle. The theory is compared with experimental results to determine a weighting factor which facilitates modeling of environmental refractive index changes using standard Mie code. Use of the optical system for characterizing nanoparticles attached to substrates for biosensing applications is discussed.
We report a new thermal targeting method in which a thermally responsive drug carrier selectively accumulates in a solid tumor that is maintained above physiological temperature by externally ...applied, focused hyperthermia. We synthesized two thermally responsive polymers that were designed to exhibit a lower critical solution temperature (LCST) transition slightly above physiological temperature: (1) a genetically engineered elastin-like polypeptide (ELP) and (2) a copolymer of
N-isopropylacrylamide (NIPAAm) and acrylamide (AAm). The delivery of systemically injected polymer–rhodamine conjugates to solid tumors was investigated by in vivo fluorescence video microscopy of ovarian tumors implanted in dorsal skin fold window chambers in nude mice, with and without local hyperthermia. When tumors were heated to 42°C, the accumulation of a thermally responsive ELP with a LCST of 40°C was approximately twofold greater than the concentration of the same polymer in tumors that were not heated. Similar results were also obtained for a thermally responsive poly(NIPAAM–co-AAm), though the enhanced accumulation of this carrier in heated tumors was lower than that observed for the thermally responsive ELP. These results suggest that enhanced delivery of drugs to solid tumors can be achieved by conjugation to thermally responsive polymers combined with local heating of tumors.
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