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Gold Nanoparticles: Colorimetric Logic Gates Based on Poly(2-alkyl-2-oxazoline)-Coated Gold Nanoparticles (Adv. Funct. Mater. 17/2015)
Abstract
A straightforward end-capping strategy is applied to synthesize xanthate-functional poly(2-alkyl-2-oxazoline)s (PAOx) that enable gold nanoparticle functionalization by a direct “grafting to” approach with citrate-stabilized gold nanoparticles (AuNPs). Owing to the presence of remaining citrate groups, the obtained PAOx@AuNPs exhibit dual stabilization by repulsive electrostatic and steric interactions giving access to water soluble molecular AND logic gates, wherein environmental temperature and ionic strength constitute the input signals, and the solution color the output signal. The temperature input value could be tuned by variation of the PAOx polymer composition, from 22 °C for poly(2-npropyl-2-oxazoline)@AuNPs to 85 °C for poly(2-ethyl-2-oxazoline)@AuNPs. Besides, advancing the fascinating field of molecular logic gates, the present research offers a facile strategy for the synthesis of PAOx@AuNPs of interest in fields spanning nanotechnology and biomedical sciences. In addition, the functionalization of PAOx with xanthate offers straightforward access to thiol-functional PAOx of high interest in polymer science.
... In order to produce PEtOx which can be linked reversibly to a CP, ethyl xanthate was used to quench the polymerization. 24 This precursor was then cleaved by aminolysis to yield thiol end groups, 25 which in turn were transferred into either reduction cleavable or non-cleavable end groups, able to be connected to CP (Schemes 1B and S1 †). ...
... However, the data followed the same trend as already shown from light scattering with a strong increase in N agg for DP ¼ 20 and signicantly longer tubes for responsive system as compared to non-responsive tubes (DP ¼ 20). Remarkably, for these tubes (24), the model had to be changed to a exible cylindrical micelle (with a Kuhn length of 400Å) to t the data appropriately. This suggests an unexpected high exibility of these supramolecular polymers in water, which could be a result of their high aspect ratio (as compared to the other compounds) in combination with the diminished sterical demand of their polymer shell. ...
... A) Haemolysis of responsive(24) and non-responsive(25) CPNT conjugates in the absence and presence of DTT (30 mM). RBCs were obtained from defibrinated donor sheep blood. ...
Cyclic peptide nanotubes (CPNT) consisting of an even number of amino acids with an alternating chirality are highly interesting materials in a biomedical context due to their ability to insert themselves into cellular membranes. However, unwanted unspecific interactions between CPNT and non-targeted cell membranes are a major drawback. To solve this issue we have synthetized a series of CPNT-polymer conjugates with a cleavable covalent connection between macromolecule and peptide. As a result, the polymers form a stabilizing and shielding shell around the nanotube that can be cleaved on demand to generate membrane active CPNT from non-active conjugates. This approach enables us to control the stacking and lateral aggregation of these materials, thus leading to stimuli responsive membrane activity. Moreover, upon activation, the systems can be adjusted to form nanotubes with an increased length instead of aggregates. We were able to study the dynamics of these systems in detail and prove the concept of stimuli responsive membrane interaction using CPNT-polymer conjugates to permeabilize liposomes as well as mammalian cell membranes.
... 10 Due to the living nature of the ω-chain end, POxs can be terminated with a variety of nucleophiles such as carboxylic acids 11,12 , amines 13,14 and thio-compounds. 15,16 Thus offering a facile way to introduce functionality to the chain end. The ability to further functionalize the α-chain end and the pendent side chain offers an incomparable level of functionalization and control over the chemical and physical properties of POx-based materials. ...
The synthesis of poly(2-oxazoline)s offers an unparalleled degree of functionalization when fabricating smart, functional polymers for biomedical uses. The termination of 2-oxazoline polymerisations by direct endcapping can be exploited to...
... The final class of terminators consists of nucleophiles based on sulfur. Thiols [4,163,191,192] and thiolates [165,193,194] are also well-known nucleophiles capable of ring-opening 2-oxazolines. Similar to its oxygen counterparts efficient termination can be achieved with the corresponding thiolate anion, such as sodium or potassium hydrogen sulfide [165,195]. ...
The design and synthesis of macromolecules, i.e. macromolecular engineering, employ specific synthetic tools for the control over the functionality, topology, and composition of a macromolecule. In terms of macromolecular engineering, 2‐oxazolines present an attractive monomer class for the design of a structurally diverse set of macromolecules, as a wide array of monomer structures can be prepared via established synthetic pathways and macromolecules have been prepared from this monomer by cationic ring‐opening, zwitterionic, anionic, and radical polymerization techniques. Most prominently applied, however, is the cationic ring‐opening polymerization, since it is compatible with a wide range of 2‐oxazoline monomers and the living polymerization mechanism allows excellent control over the macromolecular architecture throughout the different steps of the polymerization. Furthermore, the obtained poly(2‐alkyl/aryl‐2‐oxazoline)s (PAOx) display excellent physical and chemical stability, as well as an overall biocompatible nature. These factors combined have led to a recent rise in popularity of PAOx as a highly modular polymer platform in biomedicine, where cutting‐edge macromolecular engineering is applied to face current challenges in biomedicine. In this article, the current state and opportunities in the macromolecular engineering of PAOx are discussed in great detail, thereby providing an overview of the developed synthetic methodologies to control their functionality, topology, and composition.
... The thermoresponsitivity of some PAOx 32,33 (caused by their lower critical solution temperature behavior) renders them promising candidates for, e.g., optical temperature sensors 34 and molecular logic gates. 35 However, the most prominent applications for PAOx can be found in the field of biomedicine. Important examples among others are drug delivery and antifouling. ...
In this work, we present a cationic vinylimidazolium-terminated poly(2-ethyl-2-oxazoline) (PEtOx) macromonomer as a key component of gel polymer electrolytes (GPE) for lithium-ion batteries. GPE production followed a scalable process based on UV curing of the cationic PEtOx macromonomer with polyfunctional acrylic comonomers dissolved in an organic electrolyte (LP30), affording electrolyte-swollen polymeric ionic liquid (PIL) networks with PEtOx side chains. Thus, cathodes coated with a GPE layer of less than 200 μm thickness were readily manufactured. The PIL brush-type GPE is highly insoluble but swellable in LP30 and exhibits pronounced electrolyte retaining ability against evaporation. At 160 °C, the weight loss of the GPE amounted to around 5%. This is 12% less compared to an LP30-soaked commercial Celgard separator. At room temperature, the ionic conductivity was 3.6 × 10–4 S/cm, surpassing that of a comparable Celgard/LP30 system. Contrary to LP30 in Celgard, conductivity measurements for the PIL brush GPE did not indicate any crystallization of the liquid electrolyte at subambient temperatures. This was confirmed by differential scanning calorimetry, suggesting improved ionic mobility in the GPE over a wide temperature range. The electrochemical stability window of the PIL brush GPE is wide enough and fits all common lithium-ion cathode materials. In fact, the GPE exhibited exceptional oxidative stability of 5.2 V vs Li/Li⁺. Half-cell cycling experiments using a lithium iron phosphate cathode revealed high capacity values of 150 mAh/g at a current rate of C/10. When the current was increased to C/2, the capacity decreased to 120 mAh/g and the cell reached 80% of its initial capacity (referred to C/2) after 180 cycles. Thus, according to the first physicochemical and electrochemical investigations, the PEtOx-based PIL brush GPE represents a promising candidate with respect to lithium-ion battery operation.
... Nevertheless, some inspiring examples are available for iron oxide using phosphate linkers, [9] silica using trimethoxysilane linkers, [10] and gold nanoparticles using thiol linkers. [11] Herein, we combine well-established CuAAC and TE click reactions into one universal synthetic protocol for the orthogonal post-polymerization modification of triblock coPOxs aiming to generate a modular toolkit of multifunctional polymers ( Figure 1). Specific chemical functionalities can be introduced to the separated alkyne-and alkene-containing block segments in order to equip the polymer segments with charges (COOH or NH 2 ), hydroxyl groups (OH) or fluorescence labels (Rhodamine B), respectively, but also with chemical linkers. ...
Post-polymerization modification provides an elegant way to introduce chemical functionalities onto macromolecules to produce tailor-made materials with superior properties. We have adapted this concept to well-defined block copolymers of the poly(2-oxazoline) family and demonstrate the large potential of these macromolecules as universal toolkit for numerous applications. Triblock copolymers with separated water-soluble, alkyne- and alkene-containing segments were synthesized and orthogonally modified with various low-molecular weight functional molecules by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and thiol-ene (TE) click reactions, respectively. Representative toolkit polymers were used for the synthesis of gold, iron oxide and silica nanoparticles.
... Poly(2-npropyl-2-oxazoline) and poly(2-isopropyl-2-oxazoline) have reported LCSTs of 25 and 38°C [19], respectively, making them very interesting for controlled release studies. Thermoresponsive poly(2-oxazoline) coated nanoparticles have been reported as logic gates and for controlling aggregation and cellular uptake [20][21][22][23]. The hydration properties of PNIPAM shell around silica nanoparticles as a function of molecular weight were reported by Humphreys et al. [24]. ...
Temperature-responsive nanomaterials have gained increasing interest over the past decade due their ability to undergo conformational changes in situ, in response to a change in temperature. One class of temperature-responsive polymers are those with lower critical solution temperature, which phase separate in aqueous solution above a critical temperature. When these temperature-responsive polymers are grafted to a solid nanoparticle, a change in their surface properties occurs above this critical temperature, from hydrophilic to more hydrophobic, giving them a propensity to aggregate. This study explores the temperature induced aggregation of silica nanoparticles functionalised with two isomeric temperature-responsive polymers with lower critical solution temperature (LCST) behavior, namely poly(N-isopropyl acrylamide) (PNIPAM), and poly(2-n-propyl-2-oxazoline) (PNPOZ) with similar molecular weights (5,000 Da) and grafting density. These nanoparticles exhibited striking differences in the temperature of aggregation, which is consistent with LCST of each polymer. Using a combination of small-angle neutron scattering (SANS) and dynamic light scattering (DLS), we probed subtle differences in the aggregation mechanism for PNIPAM- and PNPOZ-decorated silica nanoparticles. The nanoparticles decorated with PNIPAM and PNPOZ show similar aggregation mechanism that was independent of polymer structure, whereby aggregation starts by the formation of small aggregates. A further increase in temperature leads to interaction between these aggregates and results in full-scale aggregation and subsequent phase separation.
... Aptamers exhibit an extraordinary binding specificity and affinity towards various molecules such as ions, antibiotics, proteins, and even entire cells [25][26][27][28][29][30] rendering them an ideal engineering trigger for logic operations. Although gold nanoparticles (AuNPs) have also been widely exploited as building blocks for logic operations [31][32][33][34][35], only limited attention has been paid to develop logic gates using the combination of AuNPs and aptamers. Based on the color change of AuNPs which are related to the specific interaction between targets and the aptamer, some elementary logic gates have been demonstrated [36][37][38][39][40][41]. ...
Gold nanoparticles (AuNPs) conjugated with Cy3-tagged aptamer which can specifically recognize chloramphenicol (CAP) (referred to as AuNPs-AptCAP) are described. CAP can trigger the configuration change of CAP binding aptamer, and thus switching the fluorescence of AuNPs-AptCAP through changing the efficiency of the fluorescence resonance energy transfer (FRET) system with Cy3 as donors and AuNPs as recipients. AuNPs-AptCAP exhibits a linear range of CAP concentrations from 26.0 to 277 μg L−1 with a limit of detection of 8.1 μg L−1 when Cy3 was excited at 530 nm and emission was measured at 570 nm. More importantly, AuNPs-AptCAP can be utilized as signal transducers for the build-up of a series of logic gates including YES, PASS 0, INH, NOT, PASS 1, and NAND. Utilizing the principle of a metal ion–mediated fluorescence switch together with a strong metal ion chelator, the fluorescence of AuNPs-AptCAP could be modulated by adding metal ions and EDTA sequentially. Therefore, a “Plug and Play” logic system based on AuNPs-AptCAP has been realized by simply adding other components to create new logic functions. This work highlights the advantages of simple synthesis and facile fluorescence switching properties, which will provide useful knowledge for the establishment of molecular logic systems.
Graphical abstract
... The living polymer was terminated by using potassium ethyl xanthate as a protected thiol group since thiols are extremely susceptible to the surroundings; that is why we preferred to use a protected thiol. 19 After end capping the living polymer, we can see from Cyclic PEtOx with a disulfide bond was synthesized from xanthate-PEtOx-xanthate by first reducing the xanthate groups to HS-PEtOx-SH using n-butylamine as a cleaving agent and also as a base in THF, followed by the subsequent intramolecular oxidation of the two terminal thiol groups to disulfide, affording the final cyclic PEtOx (2 K) with M n (SEC) = 1420 g mol −1 , M n (NMR) = 2250 g mol −1 , M w /M n = 1.13 and cyclic PEtOx (4 K) with M n (SEC) = 2380 g mol −1 , M n (NMR) = 4380 g mol −1 , M w /M n = 1.18, respectively. As shown in Fig. 3, the SEC measurements show a decrease in the hydrodynamic volume as a result the cyclic polymer eluted a little later although the molar masses are similar. ...
Cyclic poly(2-ethyl-2-oxazoline) (PEtOx) with degradable disulfide bond has been synthesized by combining cationic ring opening polymerization (ROP) and reversible thiol/disulfide exchange chemistry. In greater detail, a living linear PEtOx with two cationic propagating terminals was initially synthesized using 1,3-bis(bromomethyl)benzene as a difunctional initiator. Both of the two living ends of PEtOx were then reacted with potassium ethyl xanthate to afford an α,ω-xanthate end-functionalized PEtOx (Xanthate-PEtOx-Xanthate). The xanthate groups were then in-situ cleaved using n-butylamine as a cleaving agent as well as a base in the same reaction media, which produced the α,ω-thiol end-functionalized PEtOx (HS-PEtOx-SH). Cyclic polymer was eventually obtained by the successive intramolecular oxidation coupling of the thiol terminals of HS-PEtOx-SH to form a disulfide bond as a ring-closure link. For the polymeric information, ¹H NMR, SEC, MALDI-TOF-MS, and UV-visible spectroscopies were combined to characterize the linear and cyclic polymers. Ellman’s assay was used to determine the thiol content in the cyclic and thiol terminated polymers. Clean cyclic PEtOxs with number-average molar masses around 2000 (2K) and 4000 (4K) g mol⁻¹ were obtained at an unreported high polymer concentration of 5 g L⁻¹ (ca. 2.5 × 10⁻³ M for 2K polymer and ca. 1.25 × 10⁻³ M for 4K polymer) in THF. In addition, the synthetic route was compared with the intramolecular copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and proven to be more advantageous in terms of reacting concentration, yield, purification, and bonding reversibility.
... They could be potentially applied as sensors for monitoring the temperature [7,15,16]. Among those thermal responsive fluorescent polymers, poly (N-isopropylacrylamide) (PNIPAAm) [10,11,16,17], polydiacetylene (PDA) [13,15], poly(2-oxazoline) (POx) [12,18] and poly (N-vinyl caprolactam) (PVCL) [19][20][21] have attracted extensive interest of scientists. Nonetheless, there is no report up to now about thermal responsive fluorescent polymers providing a nondestructive detection of the T g [7]. ...
A novel heat-resistant fluorescent polymer poly(imino ether sulfone) (PIES) as thermally erasable and writable imaging material has been synthesized via a facile nucleophilic substitution polycondensation reaction. Taking advantage of the tenability of the “push-pull” π-electron mode by changing temperatures, the Tg of PIES film can be “naked eye” nondestructively detected by taking advantage of the visual fluorescence quenching.
... Hoogenboom and co-workers modified citrate-capped AuNPs with xanthate-functionalized poly(2-alkyl-2-oxazoline)s (PAOx) via coordination of the xanthate group to surface gold atoms. 142 The presence of the PAOx polymer brush on the surface of such particles significantly increased interparticle steric repulsion, so these AuNPs were stable toward aggregation at high ionic strength. On the other hand, this effect can be nullified upon coil-to-globule transition of PAOx polymer at elevated temperatures. ...
Accurate and precise drug delivery is the key to successful therapy. Monoclonal antibodies, which can transport therapeutic payload to cells expressing specific markers, have paved the way for targeted drug delivery and currently show tremendous clinical success. However, in those abundant cases, when a disease cannot be characterized by a single specific marker, more sophisticated drug delivery systems are required. To enhance targeting accuracy, diverse smart materials have been proposed that can also react to stimuli like variations of pH, temperature, magnetic field, etc. Furthermore, over the past few years a new category of smart materials has emerged, which can not only respond to virtually any biochemical or physical stimulus but also simultaneously analyze several cues and, moreover, can be programmed to use Boolean logic for such analysis. These advanced biocomputing agents have the potential to become a basis for future nanorobotic devices that could overcome some of the grand challenges of modern biomedicine. Here, with a brief introduction to the multidisciplinary field of biomolecular computing, we will review the concepts of nanomaterials with built-in biocomputing capabilities, which can be potentially used for drug delivery and other theranostic applications.
... Besides these three major classes of terminating agents, sodium thiolates have been introduced in 1999 as versatile functional terminating agents and were recently rediscovered to introduce, for example, carboxylic acid termini (213)(214)(215). Sodium thiolates will lead to thioethers; however if an thiol end group is desired, potassium xanthate can be used that can be transformed to a thiol after aminolysis (217,246). Furthermore, the cyclopentadiene anion has effectively been utilized to terminate the living PAOx chains and was subsequently employed for postpolymerization modification reactions via Diels-Alder chemistry (247). ...
Research in the field of poly(2‐alkyl/aryl‐2‐oxazoline)s (PAOx) is rapidly expanding as this polymer class combines high synthetic versatility with good biocompatibility, opening up the way to highly functional (bio)materials. PAOx are prepared by living cationic ring‐opening polymerization (CROP) of 2‐oxazolines. The variety of 2‐oxazoline monomers that are readily available or can easily be synthesized allows for tuning of polymer properties and introduction of diverse functionalities.
Moreover, thanks to the living nature of the CROP, well‐defined polymers with narrow molar mass distribution and high end‐group fidelity can be obtained. This article covers all aspects of PAOx ranging from the synthesis of 2‐oxazoline monomers, via an in‐depth discussion of the CROP mechanism to the synthesis and properties of functional PAOx (co)polymers. The presented research demonstrates that due to their structural adaptability and so‐called “stealth” behavior, PAOx are well‐suited for a range of biomedical applications, including polymer therapeutics, scaffolds for three‐dimensional cell culture, surface modification, matrix excipient for solid dispersions, and antimicrobial agents.The goal of this article is not to review all applications of PAOx, but to highlight key examples illustrating the numerous possibilities, broad application range and the general state‐of‐art use.
... Within the area of nanomaterials, Au NPs are widely employed as a tunable core for novel nano- structures for applications in materials science, 1 molecular transport, 2 catalysis, 3 and energy conversion. 4 Additionally, solutions of Au NPs have several useful optical properties and are used as the functional element in a wide range of applica- tions including chemical logic gates, 5 analytical chemistry of extracellular vesicles, 6 and biomedical sensing such as cancer detection. 7 Citrate-stabilized gold nanoparticles (C-Au NPs), initially developed by Turkevich et al., 8 have a number of desirable properties including high stability in aqueous solu- tions, availability of uniform quasi-spherical shape particles of up to $200 nm, 9 and high biocompatibility. ...
The ability to form complex 3D architectures using nanoparticles (NPs) as the building blocks and complex macromolecules that direct these assemblies remains a challenging objective for nanotechnology. Here we report results in which the partial substitution of classical Turkevich citrate-capped gold NPs by a novel, heteroaromatic ligand (L) results in NPs able to form coordination-driven assemblies mediated by free or protein-bound iron ions. The morphology of these assemblies can be tuned depending on the source of iron. To prove the concept, classical citrate and novel NPs were reacted with iron-containing protein hemoglobin (Hb). To diminish the influence of possible electrostatic interactions of native Hb and gold NPs, the reaction was performed at the isoelectric point of Hb. Moreover, thiol groups of Hb were protected with p-quinone to exclude thiol–gold bond formation. As expected, citrate-capped gold NPs are well dispersed in functionalized Hb, while L-functionalized NPs form assemblies. The blue shift of the Soret band of the functionalized Hb, when reacted with novel NPs, unambiguously confirms the coordination of a NP-anchored heteroaromatic ligand with the heme moiety of Hb. Coarse-grained molecular dynamics of this system were performed to gain information about aggregation dynamics and kinetics of iron- and hemoglobin-templated assemblies of L–NPs. A multi-scale simulation approach was employed to extend this model to longer time scales. The application of this model towards novel coordination-based assemblies can become a powerful tool for the development of new nanomaterials.
... But for a long time, the poly(2-oxazoline)s have not been paid much attention. In recent years, poly(2-oxazoline)s have been widely exploited for biomedical applications due to their biocompatibility [5][6][7][8], thermal responsive behavior [9][10][11] and easy chemical modification [12][13][14][15]. The living cationic ring-opening polymerization makes 2-oxazolines able to be polymerized into a well-defined polymeric structure, in which the block segment length and the end-group functionality can be finely adjusted [16]. ...
The hydrogen-bonded polymer complex thin film of poly(2-ethyl-2-oxazoline) (PEOX) and poly(acrylic acid) (PAA) was fabricated with layer-by-layer (LbL) assembly. The film shows exponential growth at early stage and transfers to linear growth after 10 assembling cycles, and the stable thickness increment per assembling cycle in the linear region could be higher than 100 nm. The film growth should be related with polymer chain diffusion during LbL assembly. The effects of assembling time, rinsing time, temperature, pH value, concentration and molecular weight on the thin film growth were investigated. Increasing the assembly time, the temperature and the concentration is favorable to produce the thick film. Prolonging rinsing time is good for preparing smooth film. The film can be constructed below pH 4.5 while the prepared film will not completely dissolve until pH value elevates to 7.0. Molecular weight has a subtle effect on the PEOX/PAA film growth. The PEOX-PAA pair that has a big molecular weight contrast shows fast film growth in the linear region.
... The ligand surface coverage (grafting density, s), the colloidal stability in pure water and in physiological buffer solution, the temperature-dependent behavior, and the interaction of the prepared NPs with solution proteins were analyzed, comparing, for the first time,core-linear and core-cyclic polymer shell NPs.T he choice of PEOXAsa ss hell-forming ligands is especially relevant, since the interest in this polymer has been rising considerably as apossible replacement for PEGs in bio/ nanomaterials preparations,i ncluding the fabrication of antifouling coatings on flat surfaces [20,21] and the synthesis of stabilizers for metallic NPs. [19,22] In addition, the use of Fe 3 O 4 cores is technologically significant, given their applicability as magnetic resonance imaging (MRI) contrast agents with low toxicity [23] and their magnetocaloric properties. [24] Notably,a ne fficient passivation of Fe 3 O 4 cores by robustly anchored and dense polymer shells prevents the generation of cytotoxic reactive oxygen species (ROS), which typically cause protein and DNAo xidation. ...
Polymere Schutzhüllen für anorganische Nanopartikel (NPs) wurden gezielt auf Haltbarkeit und Stabilität hin entworfen. E. M. Benetti et al. demonstrieren in ihrer Zuschrift (DOI: 10.1002/ange.201700196), dass cyclische Polymerliganden auf anorganischen NPs ultradichte und hoch kompakte Hüllen aus Polymerbürsten bilden. Diese NPs mit cyclischen Polymerhüllen sind deutlich stabiler als solche mit linearen Liganden und erweisen sich als vollständig biologisch inert gegenüber Serumproteinen.
... The ligand surface coverage (grafting density, s), the colloidal stability in pure water and in physiological buffer solution, the temperature-dependent behavior, and the interaction of the prepared NPs with solution proteins were analyzed, comparing, for the first time,core-linear and core-cyclic polymer shell NPs.T he choice of PEOXAsa ss hell-forming ligands is especially relevant, since the interest in this polymer has been rising considerably as apossible replacement for PEGs in bio/ nanomaterials preparations,i ncluding the fabrication of antifouling coatings on flat surfaces [20,21] and the synthesis of stabilizers for metallic NPs. [19,22] In addition, the use of Fe 3 O 4 cores is technologically significant, given their applicability as magnetic resonance imaging (MRI) contrast agents with low toxicity [23] and their magnetocaloric properties. [24] Notably,a ne fficient passivation of Fe 3 O 4 cores by robustly anchored and dense polymer shells prevents the generation of cytotoxic reactive oxygen species (ROS), which typically cause protein and DNAo xidation. ...
Cyclic poly-2-ethyl-2-oxazoline (PEOXA) ligands for superparamagnetic Fe3O4 nanoparticles (NPs) generate ultra-dense and highly compact shells, providing enhanced colloidal stability and bio-inertness in physiological media. When linear brush shells fail in providing colloidal stabilization to NPs, the cyclic ones assure long lasting dispersions. While the thermally induced dehydration of linear PEOXA shells cause irreversible aggregation of the NPs, the collapse and subsequent rehydration of similarly grafted cyclic brushes allow the full recovery of individually dispersed NPs. Although linear ligands are densely grafted onto Fe3O4 cores, a small plasma protein such as bovine serum albumin (BSA) still physisorbs within their shells. In contrast, the impenetrable entropic shield provided by cyclic brushes efficiently prevents nonspecific interaction with proteins.
... The ligand surface coverage (grafting density, s), the colloidal stability in pure water and in physiological buffer solution, the temperature-dependent behavior, and the interaction of the prepared NPs with solution proteins were analyzed, comparing, for the first time,core-linear and core-cyclic polymer shell NPs.T he choice of PEOXAsa ss hell-forming ligands is especially relevant, since the interest in this polymer has been rising considerably as apossible replacement for PEGs in bio/ nanomaterials preparations,i ncluding the fabrication of antifouling coatings on flat surfaces [20,21] and the synthesis of stabilizers for metallic NPs. [19,22] In addition, the use of Fe 3 O 4 cores is technologically significant, given their applicability as magnetic resonance imaging (MRI) contrast agents with low toxicity [23] and their magnetocaloric properties. [24] Notably,a ne fficient passivation of Fe 3 O 4 cores by robustly anchored and dense polymer shells prevents the generation of cytotoxic reactive oxygen species (ROS), which typically cause protein and DNAo xidation. ...
Cyclic poly-2-ethyl-2-oxazoline (PEOXA) ligands for superparamagnetic Fe3O4 nanoparticles (NPs) generate ultra-dense and highly compact shells, providing enhanced colloidal stability and bio-inertness in physiological media. When linear brush shells fail in providing colloidal stabilization to NPs, the cyclic ones assure long lasting dispersions. While the thermally induced dehydration of linear PEOXA shells cause irreversible aggregation of the NPs, the collapse and subsequent rehydration of similarly grafted cyclic brushes allow the full recovery of individually dispersed NPs. Although linear ligands are densely grafted onto Fe3O4 cores, a small plasma protein such as bovine serum albumin (BSA) still physisorbs within their shells. In contrast, the impenetrable entropic shield provided by cyclic brushes efficiently prevents nonspecific interaction with proteins.
... [170][171][172] Sodium thiolates will lead to thioethers however if an thiol end-group is desired …xanthate can be used which can be transformed to a thiol after aminolysis. [174] [201] Furthermore, the cyclopentadiene anion has effectively been utilized to terminate the living PAOx chains and was subsequently employed for post-polymerization modification reactions via Diels-Alder chemistry. [202] The PAOx terminated with an end group that is polymerizable can be utilized for grafting to methodologies in which a preformed functionalized PAOx or a living PAOx is coupled to the side chains of another polymer. ...
As we celebrate the 50the birthday of the discovery of poly(2-alkyl/aryl-2-oxazoline)s (PAOx) this year we see a research field that is rapidly expanding after some lesser activity in the nineties. This renewed interest in PAOx stems from the fact that this polymer class combines high synthetic versatility with good biocompatibility, opening up the way to highly functional (biocompatible) materials. PAOx are prepared by living cationic ring-opening polymerization (CROP) of 2-oxazolines, which will be the in-depth focus off this review. The variety of 2-oxazoline monomers that are readily available or can easily be synthesized, allows for tuning of polymer properties and introduction of diverse functionalities as well as provides access to different polymer architectures. Moreover, thanks to the living nature of the CROP, well-defined polymers with narrow molar mass distribution and high end-group fidelity can be obtained.
... Recently, de la Rosa et al. reported the synthesis of calorimetric logic gates based on gold nanoparticles coated with poly(2-alkyl-2-oxazoline) (PAOx) [238]. An end-capping strategy was applied to synthesize xanthate-functional PAOx that enabled a direct ''grafting to" approach with citrate-stabilized gold nanoparticles. ...
Poly(2-oxazoline)s (POx) are a class of polymers with tremendous potential for biomedical applications. The straightforward access to side and main chain functionalities by selecting suitable monomers and initiators/terminating agents, respectively, in combination with the biocompatibility, stealth and protein repellent properties of their water-soluble homologues enables the fabrication of highly functional POx materials. Post polymerisation modifications of POx further increase this toolbox and allow to merge their properties with the ones of other polymer classes. This review describes nano- and microscale POx particulate materials available to date with particular focus on macromolecular design of the polymers used for the individual formulation techniques. Amongst others, microparticles, microspheres, hollow layer-by-layer microcapsules as well as nanoparticles, micelles, polymersomes, nanogels and POx coated inorganic nanoparticles will be discussed.
... To investigate whether our findings are unique for polyNIPAm-based systems, we also coated Au NP with other polar polymers that exhibit temperature-responsive behavior (i.e. poly(methoxydiethyleneglycol acrylate) (polyDEGA; T cp % 25 8C) and poly(n-propyl-2-oxazoline) (poly n PropOx; T cp % 25 8C); [32] Figure S4; note that both polymers exhibit hysteresis in turbidimetry measurements; Figure S5) and polar polymers that are fully water-soluble over a broad temperature range (i.e. poly(N-vinylpyrrolidone); polyNVP). ...
Here we report on a simple, generally applicable method for depositing metal nanoparticles on a wide variety of solid surfaces under all aqueous conditions. Noble-metal nanoparticles obtained by citrate reduction followed by coating with thermoresponsive polymers spontaneously form a monolayer-like structure on a wide variety of substrates in presence of sodium chloride whereas this phenomenon does not occur in salt-free medium. Interestingly, this phenomenon occurs below the cloud point temperature of the polymers and we hypothesize that salt ion-induced screening of electrostatic charges on the nanoparticle surface entropically favors hydrophobic association between the polymer-coated nanoparticles and a hydrophobic substrate.
This study presents a systematic comparison of the antifouling properties of water-soluble poly(2-oxazoline) (PAOx) and poly(2-oxazine) (PAOzi) brushes grafted to gold surfaces. PAOx and PAOzi are emerging polymer classes in biomedical sciences and are being considered as superior alternatives to widely used polyethylene glycol (PEG). Four different polymers, poly(2-methyl-2-oxazoline) (PMeOx), poly(2-ethyl-2-oxazoline) (PEtOx), poly(2-methyl-2-oxazine) (PMeOzi), and poly(2-ethyl-2-oxazine) (PEtOzi), each of them in three different chain lengths, were synthesized and characterized for their antifouling properties. Results showed that all polymer-modified surfaces displayed better antifouling properties than bare gold surfaces as well as analogous PEG coatings. The antifouling properties increased in the following order: PEtOx< PMeOx∼PMeOzi<PEtOzi. The study suggests that the resistance to protein fouling derives from both surface hydrophilicity and the molecular structural flexibility of the polymer brushes. PEtOzi brushes with moderate hydrophilicity showed the best antifouling performance, possibly due to their highest chain flexibility. Overall, the research contributes to the understanding of antifouling properties in PAOx and PAOzi polymers, with potential applications in various biomaterials. This article is protected by copyright. All rights reserved.
Poly(2‐oxazoline)s are a class of organic polymers having tertiary amide groups in their chemical structure. They are currently under intense study for potential applications in many different fields due to the tunability of their physical and chemical properties. In this work, poly(2‐oxazoline)s are demonstrated for the first time as the sensing elements for chemical sensors. More specifically, a poly(2‐n‐propyl‐2‐oxazoline) (PnPropOx) with a xanthate end‐group is synthesized and used to modify a quartz crystal microbalance (QCM) transducer. The general liquid sensing properties and sensor responses of the resulting PnPropOx‐QCM sensor to a variety of ionic compounds in aqueous solutions have been evaluated revealing excellent liquid sensing properties showing a strong response to alkali chlorides and cyanides, especially. The sensor response is fast and fully reversible and the selectivity for alkali chlorides and cyanides is remarkably high. The observed sensitivity using 5 MHz PnPropOx‐QCMs reaches ≈8 Hz µM−1 at 30 °C, enabling analyte detection down to a limit of detection of 0.2 µM concentration. According to these results, it can be concluded that PnPropOx, and possibly poly(2‐oxazoline)s in general, is very promising as a sensing material for chemical sensors in liquids to selectively detect a variety of ionic species. Poly(2‐n‐propyl‐2‐oxazoline) has been applied as the sensing element in a chemical quartz crystal microbalance sensor revealing sensing responses to a variety of salts in an aqueous solution. The resulting sensor is found to have fast and reversible sensing properties showing strong responses to alkali chlorides and cyanides with sensitivity down to concentrations ≈0.2 µM.
Spiropyran-bearing telechelic poly (2-isopropyl-2-oxazoline) (SP-PiPrOx-SP) was designed as a multimodal stimuli-responsive polymer. Formed via living cationic ring-opening polymerization and ester coupling of spiropyran units, the resultant SP-PiPrOx-SP had an average molecular weight of 8.0 kDa with a narrow molecular weight distribution. SP-PiPrOx-SP exhibited a sharp hydrophilic-hydrophobic thermal transition at a specific temperature. Moreover, SP-PiPrOx-SP showed reversible photochromic changes between the colorless SP-PiPrOx-SP and purple MC-PiPrOx-MC states upon UV or visible light irradiation. The addition of DBU to MC-PiPrOx-MC resulted in the formation of a stable yellow complex that did not exhibit photochromic behavior. When CO2 was added to the yellow DBU adduct of MC-PiPrOx-MC, the solution immediately changed to purple due to the dissociation of DBU from MC-PiPrOx-MC. The addition of DBU to MC-PiPrOx-MC induced dramatic changes to the thermal transition temperature. Because SP-PiPrOx-SP simultaneously shows thermal transition, photochromic, and chemoresponsive properties, the introduction of spiropyran units has great potential for the design of functional materials.
Metal-based nanoparticles are widely used to deliver bioactive molecules and drugs to improve cancer therapy. Several research works have highlighted the synthesis of gold and silver nanoparticles by green chemistry, using biological entities to minimize the use of solvents and control their physicochemical and biological properties. Recent advances in evaluating the anticancer effect of green biogenic Au and Ag nanoparticles are mainly focused on the use of conventional 2D cell culture and in vivo murine models that allow determination of the half-maximal inhibitory concentration, a critical parameter to move forward clinical trials. However, the interaction between nanoparticles and the tumor microenvironment is not yet fully understood. Therefore, it is necessary to develop more human-like evaluation models or to improve the existing ones for a better understanding of the molecular bases of cancer. This review provides recent advances in biosynthesized Au and Ag nanoparticles for seven of the most common and relevant cancers and their biological assessment. In addition, it provides a general idea of the in silico, in vitro, ex vivo, and in vivo models used for the anticancer evaluation of green biogenic metal-based nanoparticles.
We present the synthesis development of amphiphilic, degradable poly(2-ethyl-2-oxazoline) (PEtOx) analogue block copolymers in a modular fashion utilizing the strain-promoted azide-alkyne cycloaddition (SPAAC). Subsequently to preliminary ω-end group oxidation studies by means of matrix-assisted laser desorption ionization mass spectrometry, a clickable, degradable poly(2-ethyl-2-oxazoline-stat-glycine) was synthesized via a three step post-polymerization synthesis procedure comprising the hydrolysis of azido-terminated PEtOx yielding the linear, azido-terminated poly(ethylene imine), the partial oxidation of the polymer backbone to incorporate randomly distributed glycine moieties and the re-introduction of the N-acyl ethylene imine repeating units. The azido ω-end group enabled the utilization in SPAAC. In a proof of concept approach, the degradable PEtOx analogue and its non-degradable relative were attached to a hydrophobic poly(2-n-nonyl-2-oxazoline) as well as a poly(ϵ-caprolactone) block via SPAAC. The successful conjugations were confirmed by in depth characterization utilizing NMR spectroscopy, size exclusion chromatography and matrix-assisted laser desorption ionization mass spectrometry. Due to its simplicity and flexibility the presented SPAAC approach offers numerous possibilities for the design of block copolymers comprising degradable poly(2-oxazoline) segments. This journal is
In the last decades, numerous stimuli-responsive polymers have been developed and investigated regarding their switching properties. In particular, thermoresponsive polymers, which form a miscibility gap with the ambient solvent with a lower or upper critical demixing point depending on the temperature, have been intensively studied in solution. For the application of such polymers in novel sensors, drug delivery systems or as multifunctional coatings, they typically have to be transferred into specific arrangements, such as micelles, polymer films or grafted nanoparticles. However, it turns out that the thermodynamic concept for the phase transition of free polymer chains fails, when thermoresponsive polymers are assembled into such sterically confined architectures. Whereas many published studies focus on synthetic aspects as well as individual applications of thermoresponsive polymers, the underlying structure–property relationships governing the thermoresponse of sterically constrained assemblies, are still poorly understood. Furthermore, the clear majority of publications deals with polymers that exhibit a lower critical solution temperature (LCST) behavior, with PNIPAAM as their main representative. In contrast, for polymer arrangements with an upper critical solution temperature (UCST), there is only limited knowledge about preparation, application and precise physical understanding of the phase transition. This review article provides an overview about the current knowledge of thermoresponsive polymers with limited mobility focusing on UCST behavior and the possibilities for influencing their thermoresponsive switching characteristics. It comprises star polymers, micelles as well as polymer chains grafted to flat substrates and particulate inorganic surfaces. The elaboration of the physicochemical interplay between the architecture of the polymer assembly and the resulting thermoresponsive switching behavior will be in the foreground of this consideration.
Solution‐processed organic field‐effect transistors (OFETs) have attracted great interest due to their potential as logic devices for bendable and flexible electronics. In relation to n‐channel structures, soluble fullerene semiconductors have been widely studied. However, they have not yet met the essential requirements for commercialization, primarily because of low charge carrier mobility, immature large‐scale fabrication processes, and insufficient long‐term operational stability. Interfacial engineering of the carrier‐injecting source/drain (S/D) electrodes has been proposed as an effective approach to improve charge injection, leading also to overall improved device characteristics. Here, it is demonstrated that a non‐conjugated neutral dipolar polymer, poly(2‐ethyl‐2‐oxazoline) (PEOz), formed as a nanodot structure on the S/D electrodes, enhances electron mobility in n‐channel OFETs using a range of soluble fullerenes. Overall performance is especially notable for (C60‐Ih)[5,6]fullerene (C60) and (C70‐D5h(6))[5,6]fullerene (C70) blend films, with an increase from 0.1 to 2.1 cm2 V−1 s−1. The high relative mobility and eighteen‐fold improvement are attributed not only to the anticipated reduction in S/D electrode work function but also to the beneficial effects of PEOz on the formation of a face‐centered‐cubic C60:C70 co‐crystal structure within the blend films. 18‐fold enhanced electron mobility is achieved for n‐channel organic field‐effect transistors with co‐crystalized C60:C70 blend films formed on the nanodot structured dipolar poly(2‐ethyl‐2‐oxazoline) (PEOz) interlayers that also reduce the work function of the electrodes. The PEOz nanodot layers further deliver high spatial uniformity in electron mobility and enhance device stability for transistor array fabrication.
Gold nanoparticles (GNPs) protected by poly(2-ethyl-2-oxazoline) (POZ) of different molecular weights (Mw = 5, 50, 200 and 500 kDa) were synthesised and characterised by dynamic light scattering, nanoparticle tracking analysis, zeta potential measurement and transmission electron microscopy. It was established that the use of POZ with 50 kDa resulted in formation of GNPs with low polydispersity while POZ with greater molecular weights led to formation of more polydisperse GNPs. Fluorescent labelling of these nanoparticles was achieved through their reaction with polyethyleneglycol dithiol (8-12 kDa) as a linker molecule with subsequent reaction with 6-(iodoacetamido) fluorescein. The fluorescent nature of obtained GNPs was confirmed by the appearance of the fluorescence peak at 510 nm that is typical for fluorescein molecules and glowing of the aqueous solution under the UV irradiaton. The fluorescently-labelled GNPs are promising tool in biomedical application to monitor the biological systems using fluorescent microscopy.
Gastric cancer (GC) is a multifactorial process, accompanied by alterations in metabolic pathways. Non‐invasive metabolic profiling facilitates GC diagnosis at early stage leading to an improved prognostic outcome. Herein, mesoporous PdPtAu alloys are designed to characterize the metabolic profiles in human blood. The elemental composition is optimized with heterogeneous surface plasmonic resonance, offering preferred charge transfer for photoinduced desorption/ionization and enhanced photothermal conversion for thermally driven desorption. The surface structure of PdPtAu is further tuned with controlled mesopores, accommodating metabolites only, rather than large interfering compounds. Consequently, the optimized PdPtAu alloy yields direct metabolic fingerprints by laser desorption/ionization mass spectrometry in seconds, consuming 500 nL of native plasma. A distinct metabolic phenotype is revealed for early GC by sparse learning, resulting in precise GC diagnosis with an area under the curve of 0.942. It is envisioned that the plasmonic alloy will open up a new era of minimally invasive blood analysis to improve the surveillance of cancer patients in the clinical setting. Trimetallic PdPtAu alloys with optimized elemental composition and surface structure benefit enhanced laser desorption/ionization, with photoinduced charge/energy transfer and size‐exclusive effect. By further coupling with mass spectrometry, PdPtAu alloys yield direct metabolic profiling of trace plasma in seconds. A gastric cancer (GC)‐specific metabolic phenotype is identified, shedding light on the precise and non‐invasive GC diagnosis at an early stage.
We introduce xanthate-functionalized poly(cyclic imino ethers)s (PCIEs), specifically poly(2-ethyl-2-oxazoline) and poly(2-ethyl-2-oxazine) given their stealth characteristics, as an attractive alternative to conventional thiol-based ligands for the synthesis of highly monodisperse and fluorescent gold nanoclusters (AuNCs). The xanthate in the PCIEs interacts with Au ions, acting as a well-controlled template for the direct formation of PCIE-AuNCs. This method yields red-emitting AuNCs with a narrow emission peak (λem = 645 nm), good quantum yield (4.3-4.8%), long fluorescence decay time (∼722-844 ns), and unprecedented product yield (>98%). The PCIE-AuNCs exhibit long-term colloidal stability, biocompatibility, and antifouling properties, enabling a prolonged blood circulation, lower nonspecific accumulation in major organs, and better renal clearance when compared with AuNCs without polymer coating. The advances made here in the synthesis of metal nanoclusters using xanthate-functionalized PCIEs could propel the production of highly monodisperse, biocompatible, and renally clearable nanoprobes in large-scale for different theranostic applications.
The field of molecular information handling and processing from a Boolean starting point has grown strongly during the past five years to make important contributions to the areas of intracellular computation, delivery of functional species and information security. Additionally, there has been consolidation of the original avenue of multi-input sensing devices, besides contributions to complex, multivalued and reconfigurable logic systems. Small supramolecules form the majority of these devices, though there is a strong showing from DNA and protein devices operating in a supramolecular fashion. These devices serve as our agents to perform intelligent functions which we cannot do, such as within living cells. The design and engineering of supramolecular systems is responsible for the origin of molecular logic-based computation and for its longevity.
New functional initiators for the cationic ring‐opening polymerization of 2‐alkyl‐2‐oxazolines are described to introduce a thiol moiety at the α terminus. Both tosylate and nosylate initiators carrying a thioacetate group are obtained in multigram scale, from commercial reagents in two steps, including a phototriggered thiol–ene radical addition. The nosylate derivative gives access to a satisfying control over the cationic ring‐opening polymerization of 2‐ethyl‐2‐oxazoline, with dispersity values lower than 1.1 during the entire course of the polymerization, until full conversion. Cleavage of the thioacetate end group is rapidly achieved using triazabicyclodecene, thereby leading to a mercapto terminus. The latter gives access to a new subgeneration of α‐functional poly(2‐oxazoline)s (butyl ester, N‐hydroxysuccinimidyl ester, furan) by Michael addition with commercial (meth)acrylates. The amenability of the mercapto‐poly(2‐ethyl‐2‐oxazoline) for covalent surface patterning onto acrylated surfaces is demonstrated in a microchannel cantilever spotting (µCS) experiment, characterized by X‐ray photoelectron spectroscopy (XPS) and time‐of‐flight secondary‐ion mass spectrometry (ToF‐SIMS). Tosylate‐ and nosylate‐based initiators bearing a thioacetate moiety are developed for the cationic ring‐opening polymerization of 2‐alkyloxazolines. After polymerization, diazabicycloundecene‐mediated deprotection provides well‐defined α‐mercapto‐poly(2‐ethyl‐2‐oxazoline)s, which can either serve as intermediates towards further homotelechelics or be patterned onto acrylated surfaces.
The usage of non-noble metal nanomaterials for nanoprobes or functional modules is still a big challenge because of their poor stability, functionality and surface plasmon resonance property. In this work, copper ion, mercaptosuccinic acid and nanocrystalline cellulose are combined for facile one-step synthesis and self-assembly of ultrasmall copper nanoparticles to produce super-colloidal particles ([email protected] SPs). Cu SPs show advanced multifunction for fast POCT of four metal ions (Hg²⁺, Pb²⁺, Ag⁺ and Zr⁴⁺). These selective recognitions integrate four different chemical reaction mechanisms (ion etching, core-shell deposition, templated synthesis and precipitation) to produce four distinct readout signals. The multi-signal modes-guided multianalyte sensing strategy can effectively avoid interference that affects single signal mode-based sensing. Benefiting from the creative multi-input and multi-readout abilities, the visual multi-coding logic gates of OR, NOR, AND, INHIBIT are built based on optical responses of Cu SPs.
Thin film interlayer materials inserted at the metal/semiconductor interface provide an effective means to improve charge injection and reduce the threshold voltage for organic field-effect transistors. Here, we report the use of poly(2-alkyl-2-oxazoline) interlayers for gold electrodes within n-type poly[[N,N′-bis(2-octyldodecyl)-naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl]-alt-5,5′-(2,2′-bithiophene)] field-effect transistors. We specifically show that the use of poly(2-ethyl-2-oxazoline) yields a reduction in the work function from 5.07 to 4.73 eV (ΔE = 0.34 eV), an increase in the electron mobility from 0.04 to 0.15 cm²/V s (3.75 times), and a reduction in the threshold voltage from 27.5 to 16.5 V (ΔV = 11 V) relative to bare gold. The alkyl side chain of the poly(2-alkyl-2-oxazoline) has a significant influence on the film microstructure and, as a consequence, also device performance.
While they were first reported as early as 1966, poly(2-oxazoline)s (PAOx) have made a strong resurgence in the last 20 years, mostly due to their high promises in the field of biomaterials. Telechelic PAOx constitute an important subclass because they maintain the properties of the backbone, while incorporating a defined numbers of moieties to perform a new function, access new macromolecular architectures, or anchor polymer chains to foreign objects. The current review provides a summary of the various synthetic routes to incorporate functionality at either ends of PAOx and mostly focuses on all variants utilized or newly reported since 2010, that is more than 270 new references. Particular attention is given to applications of bifunctional PAOx, that is, true telechelics.
Hyperbranched poly(2‐ethyl‐2‐oxazoline) was synthesized by a combination of cationic ring‐opening polymerization and the oxidation of thiol to disulfide groups. A three‐arm star poly(2‐ethyl‐2‐oxazoline) (PEtOx) was first synthesized using 1,3,5‐tris(bromomethyl) benzene as an initiator. The star PEtOx was end‐capped with potassium ethyl xanthate. Similarly, a linear PEtOx was synthesized and end‐capped with potassium ethyl xanthate using benzyl bromide as an initiator. Hyperbranched PEtOx was then obtained by in situ cleaving and subsequent oxidation of the star PEtOx and linear PEtOx mixture with n‐butylamine as both a cleaving agent and a base in tetrahydrofuran. The linear PEtOx was used to prevent the formation of gel. The hyperbranched PEtOx can be cleaved with dithiothreitol to trithiol and monothiol polymer. The hyperbranched PEtOx shows no remaining thiols using Ellman's assay. The resulting hyperbranched PEtOx was hydrolyzed to a novel hyperbranched polyethyleneimine with degradable disulfide linkages. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 Degradable hyperbranched PEtOx was obtained by in situ cleaving and subsequent oxidation of a mixture of star PEtOx and linear PEtOx with n‐butylamine as both a cleaving agent and a base in tetrahydrofuran. The linear PEtOx was used to prevent the formation of gel.
The precise molecular engineering of amphiphilic diblock copolymers as thermoresponsive polymer ionic liquids (PILs) couples polyisobutylene (PIB) and poly(2-ethyl-2-oxazoline) (PEtOx) blocks via an imidazolium cation. It enables thermal switching of micellar self-assembly and yields nanostructured hydrogels. Just one ionic liquid (IL)-type imidazolium cation is readily incorporated into the backbone of the PIB-IL-PEtOx block copolymers by terminating the cationic 2-ethyl-2-oxazoline (EtOx) ring-opening polymerization by alkylation of an imidazole-terminated PIB. The PEtOx block length varies as a function of the PIB-imidazole/EtOx molar ratio and governs solubility, hydrophilic/hydrophobic balance, and nanophase separation. In spite of the presence of highly hydrophobic PIB segments, PIB-IL-PEtOx are rendered water soluble with increasing PEtOx block length and form spherical and elongated micelles as well as hydrogels exhibiting wormlike nanostructures. Furthermore, the lower critical solution temperature of PEtOx segments is the key to thermoresponsive behavior of both water-soluble copolymers and copolymer hydrogels. Owing to low glass temperature and high stability of PIB, these PIB-PILs represent attractive macromolecular nanosystems enabling thermal switching of solubilization, dispersion, transport, and shuttling of molecules and nanoparticles.
In this study poly(2-ethyl-2-oxazoline) (PEOXA) chains that contains 11 mol% of benzophenone molecules was synthesized and coated on either 3-ethoxybenzophenonesilane-modified inorganic or bare organic substrates. Upon irradiation under UV light, the photo-active benzophenone molecules enabled the formation of polymer network as well as attachment of the polymer network onto the substrates. Important variables for the generation of hydrogel film with high gel content and stability, such as the heat treatment for solvent removal, the UV wavelength (that determines the irradiation energy), and the input of energy dose were varied and their influence to the gel content and stability of the hydrogel film was studied. The thickness, lifetime of benzophenone, and chemical composition of the film were determined using ellipsometry, UV/Vis spectroscopy, and XPS methods, respectively. On a film that has been exposed to physiological buffer for 14 days, XPS results indicated that chemical degradation of the copolymer did not take place. Ellipsometry results, however, indicated that some portion of the film detached and the remaining thickness was dependent on the input of energy dose during the hydrogel preparation. It was shown that when suitable conditions are applied during preparation, a stable surface-attached PEOXA-based hydrogel, i.e. approximately 78% gel content and 75–90% stability after 30 days of incubation in physiological buffer, could be generated on the surface. Dry and swollen thicknesses of the stable surface-attached film measured from AFM experiments revealed a swelling factor of 1.7. Furthermore, the AFM morphology image showed a homogenous polymer film with an average roughness of 30 nm. Protein adsorption test revealed that the resulting surface-attached PEOXA-based hydrogel film on PMMA substrate hinders BSA adsorption to the same extent as the reference system generated from benzophenone-bearing poly(dimethylacrylamide) (PDMAA).
The reversible addition–fragmentation chain‐transfer (RAFT) process represents a sophisticated polymerization technique for the preparation of tailored and well‐defined polymers from acrylates, acrylamides, and (meth)acrylates. The direct switching from other methods, such as cationic polymerizations, without the need for tedious functionalization and purification steps remains challenging. Within this study, it is demonstrated that poly(2‐oxazoline) (P(Ox)) macro chain‐transfer agents (macro‐CTAs) can be prepared through the quenching of the cationic ring‐opening polymerization with a carbonotrithioate salt. The end‐functionalization of the P(Ox)s is observed to be almost quantitative and the macro‐CTAs could be directly used for RAFT polymerization without further purification. This one‐pot procedure could be extended to a variety of (multi)block copolymers consisting of different 2‐oxazolines and acrylates with good‐to‐excellent control. Kinetic studies revealed the controlled polymerization of block copolymers, which are further accessible for α‐ and ω‐end‐functionalization. The simplicity and versatility of the approach promise a straightforward access to block copolymers from cationic and controlled radical polymerizations.
Despite some visual colorimetric chemical logic gates have been reported, a complete set of six basic logic gates have not been realized to date. Moreover, the application of the reported logic gates needs to be further extended. Herein, the label-free molybdenum oxide nanomaterials are presented for the construction of a new visual colorimetric molecular computing system. A complete set of six basic colorimetric logic gates (OR, AND, NOR, NAND, XOR, XNOR) and the INH logic gate are realized based on plasmonic switching in MoO3 nanomaterials. In addition, the rational integration of different logic gates into a 1:2 demultiplexer circuit is also testified.
Poly(2-oxazoline)s (PAOx) are of increasing importance for a wide range of applications, mostly in the biomedical field. This review describes the synthesis of 2-oxazoline monomers, their cationic ring-opening polymerization (CROP) and gives a comprehensive overview of all reported PAOx homopolymers. In the second part of the review, the polymer properties of these PAOx homopolymers with varying side-chain structures are discussed. Altogether, this review intends to serve as encyclopedia for poly(2-oxazoline)s enabling the straightforward selection of a polymer structure with the desired properties for a certain application.
Well defined 'hyperstar' copolymers were synthesized by combining hyperbranched polymers produced by thiol-yne chemistry with poly(oxazoline)s. The hyperbranched core was prepared using an AB2 monomer and a trifunctional alkene, applying a monomer feeding approach. The degree of branching was high (0.9) while maintaining low dispersities (1.3). Poly(2-ethyl-2-oxazoline) (PEtOx) functionalized with a thiol end group was coupled to the surface of the hyperbranched structure accessing terminal alkyne units. PEtOx-SH was produced by the termination of the living polymerization with ethyl xanthate and subsequent conversion to thiol under alkaline conditions. The degree of polymerization was varied producing PEtOx with 23 or 42 repeating units, respectively with a dispersity of around 1.1. After conjugation of the polymer arms, hyperstar copolymers were characterized by SEC, NMR spectroscopy, light scattering, and AFM. The polymers were able to encapsulate the hydrophobic dye Nile red within the core of the structure with loading efficiencies between 0.3 and 0.9 wt%. Cytotoxicity of the hyperstars was assessed using A2780 human ovarian carcinoma cells resulting in IC50 values of around 0.7 mg ml⁻¹. Successful internalization and colocalization with lysosomal compartments was observed by confocal microscopy studies.
Poly(2-oxazoline)s (POxs) are well-known thermo-responsive polymers that exhibit reversible hydrophilic–hydrophobic phase transitions at the lower critical solution temperature (LCST). Using living cationic ring-opening polymerisation, various functional groups can be introduced into POxs. Several clickable POxs with propargyl or azide end groups have been designed and subsequently reacted with various functional groups to prepare multifunctional POxs that respond to stimuli such as temperature, pH, chemicals and light. In this article, we briefly review recent approaches for clickable POx-based functional stimuli-responsive polymers and related applications.
Au based nanomaterials (AuNMs) are known to poessess many attractive features such as unique electrical, optical and catalytic properties as well as excellent biocompatibility. These outstanding characteristics make them promising candidates as the signal reporters, enhancement materials or others involved with bioassay, food safety and environmental monitoring. In this review, we summarize the current advancement on application of AuNMs in analytical sciences based on their local surface plasmon resonance, fluorescence and electrochemistry properties. Finally future development in this research area is also prospected.
Functionalization of biomaterials by “grafting-to” of functional polymers represents a pivotal strategy to hinder unspecific biological adhesion, provide functions to the modified biomaterials and modulate their interfacial, physico-chemical properties. The increasing interest for poly-2-alkyl-2-oxazolines (PAOXAs) as starting material for the fabrication of biomedical devices has progressively triggered the attention of chemists and materials scientists seeking possible substitutes to poly(ethylene glycol)s (PEGs) for surface functionalization. The chemical versatility of PAOXAs coupled to their stability and outstanding bioinertness when immobilized on surfaces have allowed the fabrication of coatings that efficiently prevent the contamination by proteins and bacteria.
In this review, a comprehensive summary of the surface modification methods involving the grafting of PAOXA species is provided. We especially concentrate on how the chemical tailoring of PAOXAs can be exploited to synthesize surface modifiers for the robust functionalization of different inorganic and organic materials. Additionally, a special focus is given to the performance of PAOXA coatings as biointerfaces and their comparison with PEG-based analogues. As the research efforts in finding suitable alternatives to PEGs are increasingly stimulated, among the possible solutions for meeting this demanding need PAOXAs represent one of the most promising.
This review covers the recent advances in the emerging field of thermoresponsive polyamides or polymeric amides, i.e., poly(2-oxazoline)s, polypeptoids, and polypeptides, with a specific focus on structure-thermoresponsive property relationships, self-assembly, and applications.
Well-defined polyoxazoline-silica hybrid nanoparticles were prepared by coating silica nanoparticles (SNPs) with poly(2-methyl-2-oxazoline) using a surface-initiated cationic ring-opening polymerization process. First, reverse microemulsion was used to synthesize monodisperse SNPs followed by immobilizing (chloromethyl) phenylethyl) trimethoxysilane on the surface of the nanoparticles acting as an initiator. The grafting density of the polymeric shell was controlled by varying the polymerization time, PSNPs-A, and the monomer/initiator ratio concentration, PSNPs-B. Hybrid nanoparticles were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and transmission electron microscopy (TEM). The molecular weight and polydispersity indices of the polymer chains were determined by size exclusion chromatography (SEC) after etching the silica core. The hybrid nanoparticles were further functionalized with fluorescein isothiocyanate (FITC) and folic acid (FA) as a fluorescence imaging molecule and a cancer-targeting ligand, respectively. Moreover, hybrid nanoparticles with Rubpy as a fluorophore encapsulated in the silica core and the poly(2-methyl-2-oxazoline) shell were prepared.
pH-Switchable electrochemical properties are demonstrated for the first time for native oxide-coated silicon wafer electrodes. Ultrathin and ultrathick pH-responsive poly(methacrylic acid) (PMAA) brushes, obtained by surface-initiated atom transfer radical polymerization, were used to achieve redox gating. PMAA brushes are reversibly switched between their protonated and deprotonated states by alternating acidic and basic pH, which corresponds to a swelling/collapsing behavior. As a result, the electrochemical properties of the PMAA brush-modified silicon electrode are switched "ON" and "OFF" simply by changing pH. The electrochemical properties of the modified electrode were examined by means of cyclic voltammetry and electrochemical impedance spectroscopy both in the absence and presence of ruthenium(iii) hexamine, a well-known cationic redox probe.
Here we report on a simple, generally applicable method for depositing metal nanoparticles on a wide variety of solid surfaces under all aqueous conditions. Noble-metal nanoparticles obtained by citrate reduction followed by coating with thermoresponsive polymers spontaneously form a monolayer-like structure on a wide variety of substrates in presence of sodium chloride whereas this phenomenon does not occur in salt-free medium. Interestingly, this phenomenon occurs below the cloud point temperature of the polymers and we hypothesize that salt ion-induced screening of electrostatic charges on the nanoparticle surface entropically favors hydrophobic association between the polymer-coated nanoparticles and a hydrophobic substrate.
A colorimetric sensing strategy combined with logic gates was demonstrated by taking advantage of the dispersion and aggregation of gold nanoparticles (AuNPs) on a paper-based analytical platform. By employing cytosine-Ag+-cytosine (C-Ag+-C) coordination chemistry, label-free oligonucleotide sequences (S1) could be attached to unmodified AuNPs, which on addition of S2 (complementary to S1) or silver ions (Ag+) immediately aggregated, giving rise to an OR function. Furthermore, the gate could be employed to analyze Ag+ rapidly. By taking advantage of the disparate adsorption properties of single-stranded or double-stranded DNA modified AuNPs, an INHIBIT logic gate was constructed with S1 and Ag+ as inputs to the S2-attached AuNP mixture. In addition, using the S1/S2-attached-AuNP mixture as a basic work unit and Ag+ and cysteine as two inputs, the IMPLICATION logic gate was also designed, which provided an approach for cysteine detection. The proposed logic gates with excellent selectivity toward Ag+ against other metal ions addressed concerns of low cost, simple fabrication, and easy operation, providing an attractive alternative to conventional methods, which usually involve sophisticated instruments, complicated processes, and long periods of time. More importantly, such methods exhibited high sensitivity in the detection of Ag+ in river water samples. © 2016 The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.
Fully reversible emission color change has been achieved by blending a thermoresponsive polymer with dye hybrids. The emission color can be tuned by changing the mixing ratio of each polymer-dye hybrid.
Gold nanoparticle assemblies possess diverse application potential, ranging from industrial nanotechnology to medical biotechnology. Because the structures and properties of assemblies are directly affected by the stabilization mechanism between the organic molecules serving as protecting ligands and the gold nanoparticle surface, it is crucial to find and investigate new stabilization mechanisms. Here, we report that π-conjugated phthalocyanine rings can serve as stabilizing ligands for gold nanoparticles. Bis(phthalocyaninato)lutetium(III) (LuPc2) or bis(phthalocyaninato)terbium(III) (TbPc2), even though complex, do not have specific binding units and stabilize gold nanoparticles through van der Waals interaction between parallel adsorbed phthalocyanine ligands and the gold nanoparticle surface. AC magnetic measurements and the electron-transport properties of the assemblies give direct evidence that the phthalocyanines are isolated from each other. Each nanoparticle shows weak electronic coupling despite the short internanoparticle distance (~1 nm), suggesting Efros-Shklovskii-type variable-range hopping and collective single-electron tunnelling behaviours.
The conjunction of polymers and medicine enables the development of new materials that display novel features, opening new ways to administrate drugs, design implants and biosensors, to deliver pharmaceuticals impacting cancer treatment, regenerative medicine or gene therapy. Poly(2-oxazoline)s (POx) constitute a polymer class with exceptional properties for their use in a plethora of different biomedical applications and are proposed as a versatile platform for the development of new medicine. Herein, a global vision of POx as a platform for novel biomaterials is offered, by highlighting the recent advances and breakthroughs in this fascinating field.
We cap silver, copper, and gold nanocolloids with long-chain alkylxanthates. In comparison to thiol capping, the particles are less hydrophobic and are stable in aqueous solutions for over a month, though being less stable than the corresponding oleate-capped particles. They can be transferred into relatively polar organic media (such as dichloromethane) but not into nonpolar solvents (such as dodecane). Unlike noncapped, thiol-capped, and oleate-capped colloids, they are temperature sensitive, as a result of the thermal decomposition of the xanthate molecule itself, and can be applied as thermally decomposable colloids. They demonstrate exceptional resistivity toward cyanide-induced corrosion by oxygen, when compared to noncapped or even to oleate-capped colloids. Xanthate capping enables the production of stable copper nanocolloids in aqueous solution under ambient conditions.
Gold nanoparticles have been used in biomedical applications since their first colloidal syntheses more than three centuries ago. However, over the past two decades, their beautiful colors and unique electronic properties have also attracted tremendous attention due to their historical applications in art and ancient medicine and current applications in enhanced optoelectronics and photovoltaics. In spite of their modest alchemical beginnings, gold nanoparticles exhibit physical properties that are truly different from both small molecules and bulk materials, as well as from other nanoscale particles. Their unique combination of properties is just beginning to be fully realized in range of medical diagnostic and therapeutic applications. This critical review will provide insights into the design, synthesis, functionalization, and applications of these artificial molecules in biomedicine and discuss their tailored interactions with biological systems to achieve improved patient health. Further, we provide a survey of the rapidly expanding body of literature on this topic and argue that gold nanotechnology-enabled biomedicine is not simply an act of 'gilding the (nanomedicinal) lily', but that a new 'Golden Age' of biomedical nanotechnology is truly upon us. Moving forward, the most challenging nanoscience ahead of us will be to find new chemical and physical methods of functionalizing gold nanoparticles with compounds that can promote efficient binding, clearance, and biocompatibility and to assess their safety to other biological systems and their long-term term effects on human health and reproduction (472 references).
Poly(ethylene glycol) (PEG) is the most used polymer and also the gold standard for stealth polymers in the emerging field of polymer-based drug delivery. The properties that account for the overwhelming use of PEG in biomedical applications are outlined in this Review. The first approved PEGylated products have already been on the market for 20 years. A vast amount of clinical experience has since been gained with this polymer--not only benefits, but possible side effects and complications have also been found. The areas that might need consideration and more intensive and careful examination can be divided into the following categories: hypersensitivity, unexpected changes in pharmacokinetic behavior, toxic side products, and an antagonism arising from the easy degradation of the polymer under mechanical stress as a result of its ether structure and its non-biodegradability, as well as the resulting possible accumulation in the body. These possible side effects will be discussed in this Review and alternative polymers will be evaluated.
The cloud point of copolymers of 2-ethyl-2-oxazoline and 2-n-propyl-2-oxazoline could be tuned from 25 degrees C to 100 degrees C by varying molecular weight and composition; the reversibility and concentration dependence of the cloud points were evaluated to assess the potential of these copoly(2-oxazoline)s as alternatives to poly(N-isopropylacrylamide).
A highly selective, colorimetric polynucleotide detection method based on mercaptoalkyloligonucleotide-modified gold nanoparticle
probes is reported. Introduction of a single-stranded target oligonucleotide (30 bases) into a solution containing the appropriate
probes resulted in the formation of a polymeric network of nanoparticles with a concomitant red-to-pinkish/purple color change.
Hybridization was facilitated by freezing and thawing of the solutions, and the denaturation of these hybrid materials showed
transition temperatures over a narrow range that allowed differentiation of a variety of imperfect targets. Transfer of the
hybridization mixture to a reverse-phase silica plate resulted in a blue color upon drying that could be detected visually.
The unoptimized system can detect about 10 femtomoles of an oligonucleotide.
Here we report on the preparation of well defined water-soluble poly(2-methyl-2-oxazoline) and poly(2-ethyl-2-oxazoline) terminally equipped with a chelator (N,N',N'',N'''-tetraazacylododecane-1,4,7,10-tetraacetic acid (DOTA)) for radionuclide labeling. The tissue distribution and excretion of (111)In-labeled poly(2-alkyl-2-oxazoline)s were studied in mice. We found that the hydrophilic polymers do not accumulate in tissues and are rapidly cleared from the blood pool, predominantly by glomerular filtration in the kidneys. In contrast only a small fraction is excreted via the hepatobiliary tract. Only minimal amounts of poly(2-alkyl-2-oxazoline)s are taken up by the reticuloendothelial system (RES). Scintigraphic studies revealed the feasibility of in vivo imaging of (111)In-labeled poly(2-oxazoline)s. Since additional functionalities for targeting can readily be introduced into poly(2-oxazoline)s via functional monomer units, these compounds fulfill fundamental requirements for an application as carrier molecules in radionuclide therapy.
Versatile surface coatings, which exhibit anti-fouling properties and allow one to tune surface functionality and the state of internal (macro)molecular organization, are of central importance as platforms for the study of cell-surface interactions. To enable studies of various cell characteristics, such including cell migration, proliferation and adhesion, we investigated how the mechanical properties of poly(acrylamide) (PAAm) brushes on gold can be controlled by the varying the cross-link density. Brushes and covalently cross-linked hydrogel brushes were synthesized using self-assembled monolayers (SAMs) of omega-mercaptoundecyl bromoisobutyrate (MUBiB) on gold to initiate the surface-initiated atom transfer radical polymerization (SI-ATRP) of AAm with different fractions of (MAP-methylenebis(acrylamide)) bisAAm in the feed. The polymer layers prepared with varied polymerization times or cross-linking densities were characterized by water contact angle measurements, grazing incidence reflection FTIR spectroscopy, ellipsometry and atomic force microscopy (AFM). It was found that during PAAm brush synthesis the film thickness increased markedly in early stages of the reaction, whereas after 60 min a plateau of approximately 50 nm (dry) film thickness was reached. The introduction of bisAAm into the feed resulted in reduced film thicknesses. AFM force-displacement measurements revealed that the variation of cross-linking density of polymer brush films influenced both the surface morphology and the films' nanomechanical properties. The stiffness of the polymer brush films increased with increasing fraction of bisAAm, while the swelling ratio decreased. Hence the elastic modulus of the cross-linked PAAm brushes, as determined by AFM nanoindentation, could be varied between 20 and 700 kPa, which will find application in the study of cell-surface interactions.
In recent years, the layer-by-layer (LbL) assembly based on hydrogen bonding interactions is gaining popularity for the preparation of thin film coatings, especially for biomedical purposes, based on the use of neutral, non-toxic building blocks. The use of tannic acid (TA) as hydrogen bonding donor is especially interesting as it results in LbL films that are stable under physiological conditions. In this work, investigations on the LbL thin film preparation of TA with poly(2-oxazoline)s with varying hydrophilicity, namely poly(2-methyl-2-oxazoline) (PMeOx), poly(2-ethyl-2-oxazoline) (PEtOx) and poly(2-n-propyl-2-oxazoline) (PnPropOx), are reported. The LbL assembly process is investigated by quartz crystal microbalance and UV-vis spectroscopy revealing linear growth of the film thickness. Furthermore, isothermal titration calorimetry demonstrates the LbL assembly of TA, and PMeOx is found to be mostly enthalpy driven while the LbL assembly of TA with PEtOx and PnPropOx is mostly entropy driven. Finally, scanning electron microscopy and ellipsometry demonstrate the formation of smooth thin films for LbL assembly of TA with all three polymers. Such poly(2-oxazoline) coatings have high potential for use as anti-biofouling coatings.
The article examines how versatile colorimetric logic gates can be designed based on the molecular interactions between metal ions and amino-acids using gold nanoparticles (AuNP) as the indicator. By modulating the inter-particle distance, the surface plasmon resonance (SPR) of AuNPs can be altered, along with the color change in AuNPs solutions due to the high extinction coefficients. However, most of the colorimetric logic gates reported to date suffer from limitations in complex handling procedures and time-consuming readout. Furthermore, the deficiencies in both multiple-input logic operations and integration between logic gates impede their further applications. Multi-input logic operations remain crucial in the construction of complex molecular logic gates. Theoretically, the more inputs in a logic gate system, the more complicated it would be, thus the complexity of operations increased. However, a lack of integration or concatenation between logic gates restricts their further use in real-world applications to a certain degree.
Polyethylene glycol-functionalized gold nanoparticles (PEGylated AuNPs) have been widely used as nanocarriers for the delivery of various drugs. However, little attention has been paid to whether the PEGylated AuNPs could affect the primary function of human erythrocytes, which is the main cellular component in the blood. In the current study, we show that both the deformability and oxygen-delivering ability of erythrocytes are decreased when treated with PEGyalted AuNPs of various sizes, which can be attributed to the interaction between PEGylated AuNPs and erythrocyte membranes. It is observed that the PEGylated AuNPs could also induce the aggregation of band-3 and the ATP decrease of erythrocytes. In addition, the PEGylated AuNPs can accelerate the loss of CD47 on erythrocyte membranes, possibly enhancing the senescent process of erythrocytes and the following clearance by SIRPα-expressing leukocytes in bloodstream. The results suggested that PEGylated AuNPs have the potential to affect the primary function of human erythrocytes, which should be considered when using them as drug carriers.
One of the goals of point-of-care (POC) is a chip-based, miniaturized, portable, self-containing system that allows the assay of proteins, nucleic acids, and cells in complex samples. The integration of nanomaterials and microfluidics can help achieve this goal. This tutorial review outlines the mechanism of assaying biomarkers by gold nanoparticles (AuNPs), and the implementation of AuNPs for microfluidic POC devices. In line with this, we discuss some recent advances in AuNP-coupled microfluidic sensors with enhanced performance. Portable and automated instruments for device operation and signal readout are also included for practical applications of these AuNP-combined microfluidic chips.
We report that the aqueous self-assembly behavior of citrate based gold nanoparticles decorated with the temperature responsive RAFT-based polymer poly(N-isopropylacrylamide) critically depends on the presence of salt in the medium. Both for temperature induced reversible agglomeration and for hydrogen bonding based layer-by-layer assembly with tannic acid, the presence of salt dramatically promotes the assembly behavior. We attribute this to a combination of ionic screening of the remaining citrate groups on the nanoparticle surface and a salting out effect which increases the contribution of hydrophobic interactions in the self-assembly process. These findings provide new insights into an attractive class of polymer/gold hybrid nanomaterials that can find application in biotechnology, catalysis, and biomedicine.
Biodegradable polylactic/glycolic acid copolymers are widely used as colloidal drug delivery systems. PLGA nanoparticles were prepared using non-ionic, PEO-containing block copolymer (Pluronic) and charged polymeric (PEI) surface modifiers. Physicochemical properties such as size, size distribution, zeta potential, surface composition, and colloid stability were compared to their behavior at interfaces. Adhesion of the PLGA nanoparticles to solid surface, accumulation at water surface and their cell membrane affinity (using a Langmuir lipid monolayer as a model system) were characterized. Significant differences were observed in surface activity and adhesion as well as in membrane affinity of nanoparticles depending on their surface composition. The interplay of electrostatic and steric effects resulted in sufficient colloid stability and maximum membrane affinity for the system stabilized with the mixture of Pluronic and PEI.
Gold nanoparticles stabilized by thermoresponsive polymer, poly(N-isopropylacrylamide) (PNIPAM-AuNPs), were prepared by surface grafting of thiol-terminated PNIPAM onto citrate-stabilized AuNPs. The color change of the PNIPAM-AuNPs solution from red to blue-purple without precipitation when the solution was heated to 40 ºC, above the lower critical solution temperature (LCST) of PNIPAM, indicated the thermoresponsive property of the synthesized AuNPs. PNIPAM-AuNPs were used to detect proteins by chemical nose approach based on fluorescence quenching of fluorophore by AuNPs. An array-based sensing platform for detection of six proteins, namely bovine serum albumin, lysozyme, fibrinogen, concanavalin A, hemoglobin, holo-transferrin human can be successfully developed from the PNIPAM-AuNPs having different molecular weights (4 and 8 kDa) and conformation (varied heat treatment from 25 to 40oC) in combination with a tricationic branched phenylene-ethynylene fluorophore. From Principal Component Analysis (PCA) followed by Linear Discriminant Analysis (LDA), 100% accuracy of protein classification using Leave One Out (LOO) approach can be achieved by using only two types of PNIPAM-AuNPs.
We investigate the influences that functional group, polymer molecular weight and polymer molecular architecture have on the adsorption behaviour of some sulfur containing oligo(ethylene glycol) polymers to gold. QCM-D and XPS was used in this investigation revealing that disulfide functional groups bind with more mass deposited than dithio, trithio or thiols. This was observed with small di(ethylene glycol)polymers and with higher mass polymers. The effect of the sulfo-groups was not as apparent with higher mass polymers. Longer PEG pendent chains resulted in lower binding overall on the gold surface in comparison to shorter DEG chains caused by shielding of sulfur by the longer pendent chains. Thiols undergo two steps during the adsorption process while all other sulfur species adsorb in one step. XPS revealed the dissociation of disulfide bonds when binding to gold. These findings are important when forming stable polymer films on gold efficiently, with uses in applications from bio-fouling to polymer-lipid bilayers.
The living cationic ring-opening polymerizations of 2-methyl-, 2-ethyl-, 2-nonyl-, and 2-phenyl-2-oxazoline were performed in acetonitrile at high temperatures of up to 200 degrees C in a single-mode microwave reactor. Upon enhancing the reaction rates by factors of up to 400 in the range from 80 to 200 degrees C, the first-order kinetics of the monomer consumption and the livingness of the polymerization were maintained. As a consequence of the fast, direct, and noncontact heating by the microwave irradiation, the polymerizations could be carried out in highly concentrated solutions or even from bulk conditions, yielding well-defined polymers (PDl < 1.20). Under the conditions applied in this study, a maximum number of 300 monomers (100 in the case of 2-methyl- and 2-nonyl-2-oxazoline) could be incorporated into the polymer chains under the premise that the average molecular weight distributions remained narrow (PDI < 1.20).
Novel macromonomers and telechelics of poly(2-alkyl-2-oxazoline) (PROZO) were syn-thesized by utilizing termination of propagating species (2-oxazolinium ions) in the living polymerization of 2-alkyl-2-oxazoline (ROZO) with suitable nucleophiles. Two types of p-vinylbenzyl–type macromonomers were obtained by terminating living PROZO with sodium p-vinylbenzyl alkoxide or with sodium p-vinylbenzyl mercaptide. The synthesis of telechelics having a functional group (SH, COOH) on both ends of PROZO was achieved by using a bis(2-oxazolinium salt) initiator. The PROZO dithiol was synthesized by two methods: (1) termination of the living species on both ends with NaSH, and (2) aminolysis of PROZO bis(O-ethyldithiocarbonate) given by treatment of the living PROZO with potassium O-ethyldithiocarbonate. Termination of the living PROZO with the sodium salt of di-t-butyl malonate yielded a PROZO with di-t-butyl malonate moieties on both polymer ends, from which the PROZO dicarboxylic acid was derived via free tetracarboxylic acid. © 1995 John Wiley & Sons, Inc.
A colorimetric logic gate based on free gold nanoparticles is presented with melamine and Hg(2+), as well as its colorimetric detection of Hg(2+) with good selectivity and sensitivity.
MANY properties of colloids and suspensions depend on the particle size. Series of monodisperse suspensions of the same chemical composition but of rather different particle sizes may be used to study particle size dependent phenomena, such as Brownian motion, light scattering, sedimentation and electrophoresis of small particles. We have used such series to demonstrate the increased tendency of metal suspensions to coagulate in the presence of electrolytes as the radius of the particles increases1.
Telechelic polymers, defined as macromolecules that contain two reactive end groups, are used as cross-linkers, chain extenders, and important building blocks for various macromolecular structures, including block and graft copolymers, star, hyperbranched or dendritic polymers. This review article describes the general techniques for the preparation of telechelic polymers by living and controlled/living polymerization methods; namely atom transfer radical polymerization, nitroxide mediated radical polymerization, reversible addition-fragmentation chain transfer polymerization, iniferters, iodine transfer polymerization, cobalt mediated radical polymerization, organotellurium-, organostibine-, organobismuthine-mediated living radical polymerization, living anionic polymerization, living cationic polymerization, and ring opening metathesis polymerization. The efficient click reactions for the synthesis of telechelic polymers are also presented.
Poly(2-alkyl-2-oxazoline)s are biocompatible polymers with polypeptide-isomeric structures that are attracting increasing interest as biomaterials for drug, gene, protein, and radionuclide delivery. They are, however, still relatively new in comparison to other classes of hydrophilic water-soluble polymers already established for such use, including poly(ethylene oxide), polyvinylpyrrolidone, and polymethacrylamides such as poly[N-(2-hydroxypropyl)methacrylamide]. This feature article critically compares the synthetic aspects and physicochemical and biological properties of poly(2-alkyl-2-oxazoline)s and these commonly studied polymers in terms of their suitability for biomedical applications.
A series of thermosensitive copoly(oligoethylene oxide) acrylates with narrow polydispersities were prepared by the copolymerization of oligo(ethylene oxide) acrylate and di(ethylene oxide) ethyl ether acrylate using reversible addition−fragmentation chain transfer polymerization (RAFT). These copolymers exhibit tunable LCST behavior over the range of 15−90 °C dependent on their monomer compositions. Subsequently, these copolymers were grafted onto gold nanoparticle (GNP) surfaces yielding thermosensitive gold nanoparticles. The thermoresponsive properties of these hybrid GNPs/poly(OEG-A-co-DEG-A) nanoparticles were evaluated in solution using dynamic light scattering and UV−vis spectroscopy. In addition, the susceptibility of these GNPs to protein fouling was assessed by a Bradford’s assay and found to be significantly reduced by the copolymer stabilizing layer. We also demonstrate, in a unique one-pot assembly process, the synthesis of a hybrid nanoparticle that shows dual temperature responsiveness. These hybrid nanoparticles open new applications in biotechnology and medicine.
Reversible addition-fragmentation chain transfer (RAFT) polymerization was utilized to prepare multiresponsive, self-assembling amphiphilic poly[(N,N-dimethylaminoethyl methacrylate)x-b-(N-isopropylacrylamide)y] (DMAEMAx-b-NIPAMy). Controlling block lengths, solution pH, and NaCl concentration to elicit changes in the hydrophilic mass fraction resulted in specific morphological changes upon thermally induced assembly. At y = 102 (68 wt % DMAEMA), DMAEMA165-b-NIPAM102 copolymers self-assemble into simple core−shell micelles (58 nm). Increasing y to 202 (48 wt % DMAEMA) leads to a mixture of spherical micelles (78 nm) and worm-like micelles (D = 50−100 nm, L = 400−500 nm). Further increasing y to 435 (36 wt % DMAEMA) produces vesicular structures (179 nm). Significantly, reversible assembly of these nanostructures from the present stimuli-responsive diblock copolymers can be accomplished directly in aqueous media without the necessity of dialysis or manipulation with cosolvents. Additionally, the associated nanostructures can be shell cross-linked above the critical aggregation temperature via the in situ formation of gold nanoparticles yielding assemblies with long-term aqueous stability.
The preparation of poly(N-isopropylacrylamide)-monolayer-protected clusters (PNIPAM-MPC) of gold nanoparticles was carried out in a homogeneous phase using three methods, in which three types of PNIPAM ligands were employed. The first type was comprised of PNIPAMs with narrow molar mass distributions, synthesized by reversible addition−fragmentation chain transfer (RAFT) polymerization and thus bearing a dithiobenzoate at the chain end. These polymers were used directly to passivate the gold nanoparticles upon the Schiffrin reaction in a one-pot synthesis. The second type of ligand was derived from the first one through hydrazinolysis, and they therefore contained a thiol end group. The third type of ligand was PNIPAMs obtained through conventional radical polymerization, postmodified to contain thiol end groups. The PNIPAM-MPCs were characterized by high-resolution transmission electron microscopy, UV−vis spectroscopy, and dynamic light scattering. The one-pot synthesis utilizing the ligands of the first type turned out to be a simple and facile method compared with the other two ways, with which the size of the gold nanoparticles can be easily manipulated mainly by adjusting the molar ratios of PNIPAM/HAuCl4. PNIPAM is a more efficient ligand to stabilize the gold nanoparticles in water and in organic solvents than alkanethiols. The surface density of PNIPAM chains ranged from 1.8 to 2.5 chain/nm2, which is much lower than that typical for alkanethiols. The thickness of a PNIPAM monolayer bound to the gold core is somewhat larger than the size of the random coil of the corresponding free PNIPAM in aqueous solution, which suggests that the conformation of a PNIPAM chain bound to the gold core is extended.
Infrared reflection absorption spectroscopy (IRAS) and X-ray photoelectron spectroscopy (XPS) have been used to study the adsorption of ethyl and octyl xanthate ions on metallic gold surfaces and gold surfaces sulfidized by exposure to H2S. The experimental reflection-absorption (R-A) spectra of ethyl xanthate ions adsorbed on gold are compared with the calculated R-A spectrum, which is based on the optical constants n(nu) and k(nu) derived from the KBr transmission spectrum of gold(I) ethyl xanthate. A considerable difference in relative intensities between the experimental and calculated R-A spectra is observed. At full monolayer coverage highly ordered structures are formed where the alkyl xanthate ions are coordinated to the surface through both sulfur atoms. The frequencies of the methylene stretching vibrations near 3000 cm-1 for octyl xanthate furthermore suggest that the alkyl chain has a fully extended, all trans, zigzag conformation. At submonolayer coverage the orientation and/or conformation of the xanthate ions appears to be changed and the alkyl chains of the octyl xanthate ions are also conformationally disordered. On sulfidized gold surfaces only coverages less than a monolayer could be obtained. This is probably due to blocking of the adsorption sites by adsorbed H2S. The coordination of the xanthate ions to the surface is different than for submonolayer coverages on pure gold, and the alkyl chains are conformationally disordered.
Herein we describe the surface modification of gold nanorods via the postpolymerization immobilization of polymers prepared by reversible addition−fragmentation chain transfer (RAFT). Gold nanorods have been synthesized via a three-step seed-mediated process and then subsequently modified with RAFT-preformed poly(2-(dimethylamino)ethyl methacrylate), poly(acrylic acid), and polystyrene homopolymers, with and without the use of reducing agents. Transmission electron microscopy has been used to visually monitor nanorod formations and UV−visible spectroscopy has been used to observe the absorption properties of nanorod formations. Both techniques monitored nanorods with and without surface modifications. This research provides a general and versatile technique for the surface modification of gold nanorods utilizing a wide range of polymers. Polymer modification of nanorods will potentially aid in nanorod self-assembly and ordering processes.
Self-assembly of optically active gold nanoparticles with varying generations of poly(amidoamine) (PAMAM) dendrimers provides aggregates with controlled interparticle spacing, as determined using small-angle X-ray scattering (SAXS). This structural control provides a method for systematically shifting the surface plasmon resonance (SPR) of the particles, based on the decrease in dipolar coupling with increased interparticle distance. Through choice of dendrimer generation, we were able to tune interparticle spacing over a 2.1 nm range, resulting in an 84 nm shift in the SPR. This modulation demonstrates the feasibility of using dendrimer assembly to tune the optical properties of materials.
Over the past decade, the capability of double-stranded RNAs to interfere with gene expression has driven new therapeutic approaches. Since small interfering RNA (siRNAs, 21 base pair double-stranded RNA) was shown to be able to elicit RNA interference (RNAi), efforts were directed toward the development of efficient delivery systems to preserve siRNA bioactivity throughout the delivery route, from the administration site to the target cell. Here we provide evidence of RNAi triggering, specifically silencing c-myc protooncogene, via the synthesis of a library of novel multifunctional gold nanoparticles (AuNPs). The efficiency of the AuNPs is demonstrated using a hierarchical approach including three biological systems of increasing complexity: in vitro cultured human cells, in vivo invertebrate (freshwater polyp, Hydra ), and in vivo vertebrate (mouse) models. Our synthetic methodology involved fine-tuning of multiple structural and functional moieties. Selection of the most active functionalities was assisted step-by-step through functional testing that adopted this hierarchical strategy. Merging these chemical and biological approaches led to a safe, nonpathogenic, self-tracking, and universally valid nanocarrier that could be exploited for therapeutic RNAi.
IntroductionNoble Metal Nanocomposites: the Case of AuSemiconductor Nanoparticles: Cadmium Selenide Quantum DotsMetallic Magnetic Nanoparticles: the Case of CoPerspectivesReferences
The application of the dynamic light scattering (DLS) method for determining the size distribution of colloidal gold nanoparticles in a range of 1–100 nm is discussed. It is shown that rotational diffusion of nonspherical strongly scattering particles with sizes of larger than 30–40 nm results in the appearance of a false peak in a size range of about 5–10 nm. In this case, the uncritical application of the DLS method may yield particle volume or number size distributions different from those obtained by transmission electron microscopy. For weakly scattering particles with diameters of smaller that 20 nm, the DLS method
demonstrates an additional peak of intensity distribution in the region of large sizes that is related to particle aggregates or byproduct particles rather than individual nanoparticles. Practical methods for solving the problem of false peaks are discussed. It is established that the width of the DLS distribution does not correspond to transmission electron microscopy data and is overestimated. The advantages and drawbacks of the methods are compared and it is noted that, at present, the DLS method is the only instrument suitable for nonperturbative and sensitive diagnostics of relatively slow aggregation processes with characteristic times on the order of 1 min. In particular, this method can be used to diagnose gold nanoparticle conjugate aggregation initiated by biospecific interactions on their surface.