Stimuli-responsive Copolymers Research Articles

Behavior of double stimuli-responsive copolymer of N-(3-(diethylamino) propyl)-N-methylacrylamide and N,N–diethylacrylamide in aqueous solutions

ABSTRACTDouble stimuli-responsive copolymer of N-(3-(diethylamino)propyl)-N-methylacrylamide and N,N-diethylacrylamide (molar mass M ≈ 32,000 g mol−1) in buffer solutions was studied by the static and dynamic light scattering and turbidimetry. The experiments were performed within pH interval from 7 to 13 and in a wide concentration range. Two types of scattering species were observed in solutions of all concentrations and pH at room temperatures. They were macromolecular unimers and loose aggregates. The increase in concentration and pH led to decrease in phase separation temperatures and width of phase transition.

Functionalization of Silica Microparticles with Multiple-Responsive Copolymers for Smart Controlled Chromatograph

Since its first discovery more than a century ago, chromatographic separation has become increasingly essential to organic chemistry, pharmaceuticals, proteomics, the environment, and industry. However, recent developments in basic science indicate that increasing numbers of small molecules and proteins are extremely hard to separate successfully by the traditional chromatography. Herein, we propose an intelligent chromatograph that can be controlled by various conditions such as temperature, pH, and ionic strength at the same time, which is fulfilled by the functionalization of silica microparticles with multiple stimuli-responsive copolymers, poly(N-isopropylacrylamide-co-2-(diethylamino)ethyl methacrylate-co-N-tert-butylacrylamide), by surface-initiated atom transfer radical polymerization. The intelligent chromatographic properties were evaluated in a controlled manner based on adenosine nucleotides in the aqueous mobile phase. The results indicate that the influences of temperature, pH, and mobile-ph...

Versatile Encapsulation Technology Based on Tailored pH-Responsive Amphiphilic Polymers: Emulsion Gels and Capsules.

We present a multipurpose technology to encapsulate hydrophobic substances in micron-sized emulsion droplets and capsules. The encapsulating agent is a comblike stimuli-responsive copolymer comprising side-chain surfactants attached to a methacrylic acid/ethyl acrylate polyelectrolyte backbone. The composition and structure of the hydrophobic moieties of the side chains are customized to tune the particle morphology and the processing conditions. The technology exploits the synergy of properties provided by the copolymer: interfacial activity, pH responsiveness, and viscoelasticity. A one-pot process produces emulsion gels or capsule dispersions consisting of a hydrophobic liquid core surrounded by a polymer shell. The dispersions resist high ionic strengths and exhibit long-term stability. The versatility of the method is demonstrated by encapsulating various hydrophobic substances covering a broad range of viscosities and polarities-conventional and technical oils, perfumes, and alkyd paints-with a high degree of morphological and rheological control.

Dual stimuli-responsive Fe3O4 graft poly(acrylic acid)-block-poly(2-methacryloyloxyethyl ferrocenecarboxylate) copolymer micromicelles: surface RAFT synthesis, self-assembly and drug release applications

BackgroundStimuli-responsive polymer materials are a new kind of intelligent materials based on the concept of bionics, which exhibits more significant changes in physicochemical properties upon triggered by tiny environment stimuli, hence providing a good carrier platform for antitumor drug delivery.ResultsDual stimuli-responsive Fe3O4 graft poly(acrylic acid)-block-poly(2-methacryloyloxyethyl ferrocenecarboxylate) block copolymers (Fe3O4-g-PAA-b-PMAEFC) were engineered and synthesized through a two-step sequential reversible addition-fragmentation chain transfer polymerization route. The characterization was performed by FTIR, 1H NMR, SEC, XRD and TGA techniques. The self-assembly behavior in aqueous solution upon triggered by pH, magnetic and redox stimuli was investigated via zeta potentials, vibration sample magnetometer, cyclic voltammetry, fluorescent spectrometry, dynamic light scattering, XPS, TEM and SEM measurements. The experimental results indicated that the Fe3O4-g-PAA-b-PMAEFC copolymer materials could spontaneously assemble into hybrid magnetic copolymer micromicelles with core–shell structure, and exhibited superparamagnetism, redox and pH stimuli-responsive features. The hybrid copolymer micromicelles were stable and nontoxic, and could entrap hydrophobic anticancer drug, which was in turn swiftly and effectively delivered from the drug-loaded micromicelles at special microenvironments such as acidic pH and high reactive oxygen species.ConclusionThis class of stimuli-responsive copolymer materials is expected to find wide applications in medical science and biology, etc., especially in drug delivery system.

Probing Single-Molecule Adhesion of a Stimuli Responsive Oligo(ethylene glycol) Methacrylate Copolymer on a Molecularly Smooth Hydrophobic MoS2 Basal Plane Surface.

Molybdenum disulfide (MoS2) has been receiving increasing attention in scientific research due to its unique properties. Up to now, several techniques have been developed to prepare exfoliated nanosize MoS2 dispersions to facilitate its applications. To improve its desired performance, as-prepared MoS2 dispersion needs further appropriate modification by polymers. Thus, understanding polymer-MoS2 interaction is of great scientific importance and practical interest. Here, we report our results on molecular interactions of a biocompatible stimuli-responsive copolymer with the basal plane surface of MoS2 determined using single molecule force spectroscopy (SMFS). Under isothermal conditions, the single-molecule adhesion force of oligo(ethylene glycol) methacrylate copolymer was found to increase from 50 to 75 pN with increasing NaCl concentration from 1 mM to 2 M, as a result of increasing hydrophobicity of the polymers. The theoretical analysis demonstrated that single-molecule adhesion force is determined by two contributions: the adhesion energy per monomer and the entropic free energy of the stretched polymer chain. Further data analysis revealed a significant increase in the adhesion energy per monomer with a negligible change in the other contribution with increasing salt concentration. The hydrophobic attraction (HA) was found to be the main contribution for the higher adhesion energy in electrolyte solutions of higher NaCl concentrations where the zero-frequency of van der Waals interaction were effectively screened. The results illustrate that oligo(ethylene glycol) methacrylate copolymer is a promising polymer for functionalizing MoS2 and that one can simply change the salt concentration to modulate the single-molecule interactions for desired applications.

Using Dynamic Covalent Chemistry To Drive Morphological Transitions: Controlled Release of Encapsulated Nanoparticles from Block Copolymer Vesicles.

Dynamic covalent chemistry is exploited to drive morphological order–order transitions to achieve the controlled release of a model payload (e.g., silica nanoparticles) encapsulated within block copolymer vesicles. More specifically, poly(glycerol monomethacrylate)–poly(2-hydroxypropyl methacrylate) (PGMA–PHPMA) diblock copolymer vesicles were prepared via aqueous polymerization-induced self-assembly in either the presence or absence of silica nanoparticles. Addition of 3-aminophenylboronic acid (APBA) to such vesicles results in specific binding of this reagent to some of the pendent cis-diol groups on the hydrophilic PGMA chains to form phenylboronate ester bonds in mildly alkaline aqueous solution (pH ∼ 10). This leads to a subtle increase in the effective volume fraction of this stabilizer block, which in turn causes a reduction in the packing parameter and hence induces a vesicle-to-worm (or vesicle-to-sphere) morphological transition. The evolution in copolymer morphology (and the associated sol–gel transitions) was monitored using dynamic light scattering, transmission electron microscopy, oscillatory rheology, and small-angle X-ray scattering. In contrast to the literature, in situ release of encapsulated silica nanoparticles is achieved via vesicle dissociation at room temperature; moreover, the rate of release can be fine-tuned by varying the solution pH and/or the APBA concentration. Furthermore, this strategy also works (i) for relatively thick-walled vesicles that do not normally exhibit stimulus-responsive behavior and (ii) in the presence of added salt. This novel molecular recognition strategy to trigger morphological transitions via dynamic covalent chemistry offers considerable scope for the design of new stimulus-responsive copolymer vesicles (and hydrogels) for targeted delivery and controlled release of cargoes. In particular, the conditions used in this new approach are relevant to liquid laundry formulations, whereby enzymes require protection to prevent their deactivation by bleach.

Rational Design of a Stimuli-Responsive Polymer Electrode Interface Coupled with in Vivo Microdialysis for Measurement of Sialic Acid in Live Mouse Brain in Alzheimer's Disease.

Sensitive and selective monitoring of sialic acid (SA) in cerebral nervous system is of great importance for studying the role that SA plays in the pathological process of Alzheimer's disease (AD). In this work, we first reported an electrochemical biosensor based on a novel stimuli-responsive copolymer for selective and sensitive detection of SA in mouse brain. Notably, through synergetic hydrogen-bonding interactions, the copolymer could translate the recognition of SA into their conformational transition and wettability switch, which facilitated the access and enrichment of redox labels and targets to the electrode surface, thus significantly improving the detection sensitivity with the detection limit down to 0.4 pM. Besides amplified sensing signals, the proposed method exhibited good selectivity toward SA in comparison to potential interference molecules coexisting in the complex brain system due to the combination of high affinity between phenylboronic acid (PBA) and SA and the directional hydrogen-bonding interactions in the copolymer. The electrochemical biosensor with remarkable analytical performance was successfully applied to evaluate the dynamic change of SA level in live mouse brain with AD combined with in vivo midrodialysis. The accurate concentration of SA in different brain regions of live mouse with AD has been reported for the first time, which is beneficial for progressing our understanding of the role that SA plays in physiological and pathological events in the brain.

Multifunctionalization of Poly(vinylidene fluoride)/Reactive Copolymer Blend Membranes for Broad Spectrum Applications.

Simultaneous immobilization and cross-linking of antifouling/low toxic polymers, e.g., poly(ethylenimine) (PEI), dextran (Dex), agarose (Agr), poly(ethylene glycol) (PEG), PEI-Dex, and PEI-PEG conjugates, and stimuli-responsive copolymers on a porous membrane surface in mild reaction conditions is desirable for the enhancement of hydrophilicity, antifouling character, cytocompatibility, and inducing stimuli-responsive behavior. Grafting to technique is required since the precursors of most of these macromolecules are not amenable to surface-initiated polymerization. In this work, we report a versatile process for the simultaneous immobilization and cross-linking of a library of macromolecules on and into the blend membrane (PVDF-blend) of poly(vinylidene fluoride) and poly(methyl methacrylate)-co-poly(chloromethylstyrene). Sequential nucleophilic substitution reaction between activated halide moieties of the copolymer and amine groups of different macromolecules readily provided series of modified membranes. These membranes exhibited antifouling property superior to that of the unmodified membrane. The effectiveness of this technique has been demonstrated by the immobilization of pH or both pH- and temperature-responsive copolymer on PVDF-blend membrane for responsive separation of poly(ethylene oxide) and bovine serum albumin. Silver nanoparticles were also anchored on the select modified membranes surfaces for the enhancement of antibiofouling property. Our approach is useful to obtain verities of functional membranes and selection of membrane for a particular application.

Smart Nanovalves with Thermoresponsive Amphiphilic Triblock Copolymer Brushes

ABSTRACTNanochannels modified with stimuli-responsive copolymer brushes offer a smart nanovalve mechanism. The potential application of these special nanovalves is wide-ranging and includes the areas of drug delivery and signal transduction, as well as molecular machines. In this study, molecular dynamics simulations were performed to study nanovalve systems that use thermo-responsive amphiphilic triblock copolymer brushes grafted onto the surface of the nanochannel. Varying the system temperature facilitated the extension/collapse transition of the copolymer brushes, which resulted in the opening/closing of the nanochannels. The results of the investigation of the effect of the grafting density and the composition of the copolymers on the conformational transition behavior showed that the composition of copolymer has a significant influence on the nanovalve system. A remarkable result is the effectiveness of the use of intermediate or relatively low grafting density in obtaining an ideal controlling effect on the nanochannels. Our work provides a fundamental understanding of nanovalves that utilize thermo-responsive copolymers, and guidance for the design of a smart nanochannel.

Design and synthesis of redox and oxidative dual responsive block copolymer micelles for intracellular drug delivery

The need for smart materials in the area of biotechnology has accelerated the development of stimuli-responsive copolymer micelles. Here, we reported a novel dual-stimuli-responsive block copolymer PEG-DMTK-SS-PLA with both dimethyl thioketal (DMTK) and disulfide linkage incorporated into the backbone, capable of triggering fast drug release properties upon both oxidative (H2O2) and reductive (GSH) environment. The CMC values of these copolymer micelles ranging from 0.051 to 0.087mgmL−1, the average diameters are from 34nm to 55nm and 65nm to 198nm for blank and DOX-loaded micelles respectively. MTT assay conducted in NIH 3T3 cells showed the low cytotoxicity of these micelles even when the concentration reached up to 500μg/mL. Considering tumor microenvironment’s diverse in kinds of tumor cells, fluorescence microscopy, flow cytometry and MTT activity analysis were conducted in several cancer cells (e.g., cervix, lung, gastric, and colon cancer cells), and further confirmed that the dual responsive PEG-DMTK-SS-PLA micelles were degraded much faster than that of non-responsive PEG-PLA and single responsive PEG-SS-PLA and PEG-DMTK-PLA micelles. These results indicate that the dual-responsive micelles are promising for efficient anticancer drug delivery.

Multi-responsive (diethylene glycol)methyl ether methacrylate (DEGMA)-based copolymer systems

RAFT polymerisation was used to synthesise stimuli-responsive DEGMA-based copolymer systems, and their solution properties and aggregation behaviour were then studied.

Self-organization of hydrophobic-capped triblock copolymers with a polyelectrolyte midblock: a coarse-grained molecular dynamics simulation study.

We present the results of a Langevin dynamics simulation study of micellar organization and hydrogel formation in the solutions of coarse-grained ABA copolymer chains. Polymer chains are modeled as bead-spring chains of Lennard-Jones particles by explicit treatment of ionic species in implicit solvent. The studied copolymer is composed of a polyelectrolyte midblock flanked by two hydrophobic endblocks. We explore the self-assembly of copolymer solutions at a fixed polymer concentration and temperature upon systematic variation of the midblock charge fraction, valency of neutralizing counterions, and the stiffness and length of hydrophobic endblocks. Minimization of the surface energy, conformational entropy of the midblock chains, electrostatic repulsion of midblock charges, and the translational entropy of counterions are found to play central roles in controlling the self-organization features of copolymer solutions. Flower-like micelles with A-blocks forming the core of spherical aggregates and B-blocks constituting the micelle corona are established for the neutral midblocks. Increasing the charge content of B chains lowers the fraction of loop conformations and yields a spanning hydrogel network with midblocks bridging the hydrophobic clusters. Counterion valence is shown to exert a strong effect on the micelle size and network structure. The increase in the rigidity of terminal A-blocks increases the fraction of bridging chains and results in the formation of a hydrogel network with bundle-like hydrophobic domains. Longer endblocks are shown to increase the hydrophobic cluster size and enhance the bridged midblock fraction. The qualitative agreement between the experimental and theoretical studies is also discussed. The comprehensive molecular picture provides a framework for the future studies of stimuli-responsive copolymer systems.

Cationic effect of an ionic copolymer with a temperature-responsive charateristic on the LCST value: A broad LCST spectrum of 35 to 46 °C

A series of stimuli-responsive copolymers (p-NIBIm) of N-isopropylacrylamide (NIPAAm) and 1-butyl-3-vinyl imidazolium bromide (BVIm) with various BVIm monomer concentrations such as 5, 10, 15, and 20 mol% were synthesized by radical copolymerization. The different concentrations of the imidazolium moiety within the resulted copolymer chain were determined by 1H NMR analysis. The LCST (lower critical solution temperature) values of the copolymers that were checked by UV-Vis spectrophotometer increased with the increasing concentration of the imidazolium moiety and were ranged from 36 up to 46 °C. According to the increasing concentration of the imidazolium moiety, the p-NIBIm copolymers also showed increasing zeta potential values (from +3.4 up to +21.3 mV) at pH 7, increasing initial and final micelle sizes (from 211.5 to 69.1 and from 325.4 to 171.2 nm), respectively, at 25 and 50 °C, and increasing contraction levels of micelle volumes between 25-50 °C (from 2.69×10-18 up to 8.67×10-18 cm3). These results demonstrate that it is possible to tune the LCST value of a temperature-responsive copolymer only by changing the imidazolium unit (BVIm) concentration within the copolymer chain. Moreover, p-NIBIm10 and 15 among the prepared copolymers could demonstrate high applicability in various endeavors such as on a target drug or in a gene delivery system.

Dual stimuli-responsive copolymers comprising poly(N-isopropylacrylamide) and poly(cyano malachite green)

Abstract This article describes synthesis and stimuli-responsive behavior of dual stimuli-responsive copolymers (PNIMG) composed of temperature-responsive poly( N -isopropylacrylamide) (NIPAAm) and photo-responsive poly(cyano malachite green) (CMG). The PNIMG copolymer was regularly and uniformly layer-by-layer deposited with poly(acrylic acid) (PAA) onto solid substrates via hydrogen bonding between carboxylic acid group of PAA and amide hydrogen of PNIPAAm in PNIMG, leading to multilayered films composed of PNIMG/PAA bilayers. Upon UV irradiation, the colorless electrically neutral CMG involved in PNIMG copolymer in solution and multilayer films was converted to the light green cationic form through the release of cyanide ion. The initial photoionization rates of PNIMG-3, PNIMG-6 and PNIMG-10 (numbers denote the mol% CMG composition in PNIMG) in solution were determined to 6.54 × 10 −3 , 1.88 × 10 −2 and 3.22 × 10 −2 s −1 , respectively, indicating the strong dependency of the photoionization rate on the CMG compositions of PNIMG. The photoionization rates of CMG in (PNIMG-3/PAA) 10 and (PNIMG-6/PAA) 10 multilayer films were determined to be 6.50 × 10 −5 and 1.25 × 10 −4 s −1 , respectively, which were slower by two orders of magnitude, compared to those in solution. The thermal-responsive behavior of PNIMGs in solution was manifested from clear identification of their lower critical solution temperature (LCST), which was dependent on the CMG composition of PNIMG. The LCST of PNIMG-3, PNIMG-6 and PNIMG-10 copolymers (29, 28 and 27.5 °C, respectively) decreased gradually, as the CMG composition increased. By contrast, the PNIMG copolymers positively-charged after the UV irradiation exhibited very slow and weak phase transition behavior in acetate buffer solution, leading to no clear identification of their LCSTs. The multilayer film composed of PNIMG/PAA bilayers involving the net and fixed positive CMG charges acts as a Donnan membrane, which exerts either weak electrostatic repulsion or attraction effects for cations and anions. The selectivity of K + /Ca 2+ by (PNIMG-6/PAA) 10 membrane increased nearly by twofold compared to that of (PNIMG-3/PAA) 10 , exhibiting the influence of CMG density on the Donnan effect of the membranes. Furthermore, the selectivity of K + /Ca 2+ by (PNIMG/PAA) 10 membranes showed 2–3 fold increase after UV irradiation due to the enhanced Donnan effect. These photo-responsive membranes would find potential applications in designing sophisticated modern materials for biotechnology, filtration systems, and sensors, which could require a remote, clean and focused photocontrol over ions or particle-transports.

Synthesis and Self-Assembly of CO2–Temperature Dual Stimuli-Responsive Triblock Copolymers

Poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) with a β-cyclodextrin (β-CD) at the chain end was synthesized via atom transfer radical polymerization (ATRP); poly(e-caprolactone) (PCL) with a −C═C– segment and an adamantane (Ada) group at two ends, respectively, was prepared through ring-opening polymerization (ROP), and poly(N-isopropylacrylamide) (PNIPAM) with a −S–C(S)–S– segment, which can be converted into a thiol group, was yielded by reversible addition–fragmentation chain transfer polymerization (RAFT). A supramolecular triblock stimuli-responsive copolymer PNIPAM-b-PCL-b-PDMAEMA having good biocompatibility with PNIPAM and PDMAEMA hydrophilic segments and PCL hydrophobic segment was constructed by thiol–ene Michael addition and host–guest interaction. The triblock copolymer could self-assemble into vesicles and respond to carbon dioxide (CO2) gas and temperature reversibly. Under the stimulation of CO2, the vesicular assemblies swelled obviously; while raising the temperature from 25 to 40 °...

Rapid self-healing and triple stimuli responsiveness of a supramolecular polymer gel based on boron–catechol interactions in a novel water-soluble mussel-inspired copolymer

Marine and freshwater mussels secrete proteinaceous adhesive materials for adherence to the substrates upon which they reside. It is well known that 3,4-dihydroxyphenylalanine (DOPA) is the key to understanding these mussel adhesive proteins (MAPs). In order to gain a better understanding of their complex formation and quick recovery upon rupturing, novel water soluble copolymers of N-isopropylacrylamide and dopamine methacrylate were synthesized in such a way that they have 1, 2.5, and 5 mole percent dopamine monomer with respect to the NIPAM monomer on average. The statistical distribution of DOPA-functionalities along the chain makes the material a close synthetic equivalent of the byssal thread proteins of mytili. At acidic pH, the aqueous copolymer solution behaves like an unentangled copolymer solution, but at basic pH, these catechol functionalities form a dicomplex with H3BO3, thereby crosslinking two chains, proven by 11B-NMR and gelation. The polymer solution is thermosensitive with a pH-dependent lower critical solution temperature (LCST) between 21 and 33 °C, depending on the DOPA-content. If 2 or more functionalities per chain are present, a gel is formed that is self-healing with very quick recovery from sustained damage. The moduli of the gels depend on the concentration of functionalities. Hence, triple stimuli responsive copolymers were obtained.

Chemical force microscopy of stimuli-responsive adhesive copolymers

Atomic force microscopy with chemically sensitive tips was used to investigate the hydrophobic and electrostatic interaction forces of a stimuli-responsive adhesive polymer, and their dynamic changes in response to water immersion and salt concentration. Block copolymer-filled coatings were obtained by incorporating an amphiphilic block copolymer containing a polydimethylsiloxane (PDMS) block and a poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) block in a PDMS matrix. Topographic images of fresh samples revealed the presence of nanoscale domains associated with the presence of copolymers, covered by a thin layer of PDMS. Prolonged (30 days) immersion in aqueous solution led to the exposure of the hydrophilic PDMAEMA chains on the surface. Using adhesion force mapping with hydrophobic tips, we showed that fresh samples were uniformly hydrophobic, while aged samples exhibited lower surface hydrophobicity and featured nanoscale hydrophilic copolymer domains. Force mapping with negatively charged tips revealed remarkable salt-dependent force plateau signatures reflecting desorption of polyelectrolyte copolymer chains. These nanoscale experiments show how solvent-induced conformational changes of stimuli-responsive copolymers can be used to modulate surface adhesion.

Thermo- and pH-responsive copolymers based on PLGA-PEG-PLGA and poly(l-histidine): Synthesis and in vitro characterization of copolymer micelles

A series of novel thermo- and pH-responsive block copolymers of PHis-PLGA-PEG-PLGA-PHis composed of poly(ethylene glycol) (PEG), poly(d,l-lactide-co-glycolide) (PLGA) and poly(l-histidine) (PHis) were synthesized and used for the construction of stimuli-responsive copolymer micelles. The starting polymers of PLGA-PEG-PLGA and PHis were synthesized by ring-opening polymerization of dl-lactide and glycolide with PEG as an initiator and l-histidine N-carboxylanhydride with isopropylamine as an initiator, respectively. The final copolymer was obtained by the coupling reaction of PHis with PLGA-PEG-PLGA. The copolymer micelles were constructed to have an inner core consisting of two hydrophobic blocks (PLGA and deprotonated PHis) and an outer hydrophilic PEG shell. The temperature- and pH-induced structure changes of the micelles were characterized by an alteration in particle size, a decrease in pyrene florescence intensity, and a variation of 1H NMR spectra in D2O. It was speculated that the hydrophobic–hydrophilic transitions of PEG and PHis in response to temperature and pH variations accounted for the destabilization of micelles. In vitro release profiles, cell cytotoxicity and intracellular location studies further confirmed the temperature- and pH-responsive properties of the copolymer micelles. These results demonstrate the potential of the developed copolymers to be stimuli-responsive carriers for targeted delivery of anti-cancer drugs.

Organic-Inorganic Hybrid Nanoparticles via Photoinduced Micellation and Siloxane Core Cross-Linking of Stimuli-Responsive Copolymers.

Photoacid-induced siloxane cross-linking of stimuli-responsive copolymer micelles allows the synthesis of well-defined organic-inorganic hybrid nanoparticles. Two conceptually different synthetic approaches are presented, both via photoinduced cross-linking of poly(4-hydroxystyrene-block-styrene) micelles and via one-pot photoacid-catalyzed micelle formation and siloxane cross-linking of poly(4-tert-butoxystyrene-block-styrene). The multistep synthetic route showed intermicellar cross-linking leading to agglomerates. In contrast to this, the formation of the nanoparticles via the one-pot synthesis yielded well-defined structures. The use of different siloxane cross-linking agents and their effects on the properties of the cross-linked micellar structures have been evaluated. Scanning electron microscopy and differential scanning calorimetry indicate rigid core cross-linked nanoparticles. Their size, molar mass, and swelling behavior were analyzed by dynamic and static light scattering. Cyclic siloxane cross-linking agents lead to residual C═C double bonds within the nanoparticle core that allow postsynthetic modification by, e.g., thiol-ene click reactions.

Stimuli-responsive copolymer solution and surface assemblies for biomedical applications.

Stimuli-responsive polymeric materials is one of the fastest growing fields of the 21st century, with the annual number of papers published more than quadrupling in the last ten years. The responsiveness of polymer solution assemblies and surfaces to biological stimuli (e.g. pH, reduction-oxidation, enzymes, glucose) and externally applied triggers (e.g. temperature, light, solvent quality) shows particular promise for various biomedical applications including drug delivery, tissue engineering, medical diagnostics, and bioseparations. Furthermore, the integration of copolymer architectures into stimuli-responsive materials design enables exquisite control over the locations of responsive sites within self-assembled nanostructures. The combination of new synthesis techniques and well-defined copolymer self-assembly has facilitated substantial developments in stimuli-responsive materials in recent years. In this tutorial review, we discuss several methods that have been employed to synthesize self-assembling and stimuli-responsive copolymers for biomedical applications, and we identify common themes in the response mechanisms among the targeted stimuli. Additionally, we highlight parallels between the chemistries used for generating solution assemblies and those employed for creating copolymer surfaces.