Stimuli-responsive Block Copolymers Research Articles

Photo and pH dual stimuli-responsive block copolymer micelles with defined incorporation of o-nitrobenzyl units in poly(ɛ-caprolactone) block for controlled release

A series of dual stimuli-responsive block copolymers with varying content of photocleavable o-nitrobenzyl (ONB) ester group pendent in the hydrophobic poly(ɛ-caprolactone) block and pH-cleavable acetal linkage at the junction with hydrophilic poly(ethylene glycol) block is synthesized. The hydrophobic block is a random copolymer synthesized by ring-opening copolymerization of ɛ-caprolactone and ONB-substituted ɛ-caprolactone containing varying compositions of the two monomers. Kinetics of polymerization shows that ONB-functionalized monomer has lower reactivity than that of the unsubstituted monomer. The series of block copolymers shows self-assembly into well-defined spherical micelles of average size of 150–200 nm in aqueous solution. Photocleavage of ONB groups is studied by NMR and UV–vis spectroscopy, and its extent is determined. The two stimuli viz. UV light and pH are used individually as well as simultaneously to study the controlled release of the encapsulated drug Camptothecin and the synergistic effect of the two stimuli is demonstrated. The effect of varying content of ONB groups is observed on drug release profile. MTT assay showed non-cytotoxic nature of the polymer. Cell uptake and photoinduced release of doxorubicin (DOX) from the micelles in MDA-MB-231 cells is demonstrated.

Light-Triggered Reversible Swelling of Azobenzene-Containing Block Copolymer Worms via Confined Deformation Prepared by Polymerization-Induced Self-Assembly.

Stimuli-responsive block copolymer nanoparticles (NPs) have received close attention in recent years owing to their tremendous application potential in smart materials. Azobenzene-containing NPs are widely studied due to the advantages of light as a stimulus and fast reversible trans-cis isomerization of azobenzene chromophores. However, the inefficient preparation process and difficult reversible transformation of morphologies limit their development. Herein it is demonstrated that the light-triggered reversible swelling behavior of wormlike NPs with high azobenzene content could be realized via confined deformation. These worms are prepared in large quantities via polymerization-induced self-assembly based on the copolymerization of 11-(4-(4-butylphenylazo)phenoxy)undecyl methacrylate (MAAz) and N-(methacryloxy)succinimide (NMAS) monomers. Upon UV/visible light irradiation, the reversible deformation of worms is achieved when the feed molar ratio of NMAS/MAAz is relatively high or via crosslinking using diamines, which leads to the reduction of the photoisomerization efficiency. The diameter variation of the worms is influenced by the amount and types of crosslinkers. Moreover, the scalability of this strategy is further proved by the fabrication of photo- and reductant-responsive crosslinked worms. It is expected that this study not only provides a new route to affording reversible photoresponsive NPs but also offers a unique insight into the reversible photodeformation mechanism of azobenzene-containing NPs.

Reconfigurable dual-mode optical encryption enabled by block copolymer photonic crystal with micro-imprinted holographic metasurface

Dual-mode optical encryption based on holographic metasurfaces and color components is of great attraction because of their enhanced information security and storage; however, the realization of independently as well as reversibly encodable holographic metasurfaces and color components remains unreported. Herein, we present reconfigurable dual-mode encryptions of structural colors (SC) and holograms, achieved through stimuli-responsive block copolymer (BCP) photonic crystals (PCs) with micro-imprinted holographic metasurfaces. Holographic images appear when the micro-imprinted BCP PCs, consisting of self-assembled alternating lamellae of two dielectrics, are exposed to an incident laser. A characteristic SC develops in the visible range when the imprinted film is immersed in a liquid agent that can swell one of the dielectrics, allowing for dual-mode holographic and SC encodings in the solid and liquid states, respectively. The dual-mode optical encoding is reconfigured. The holographic image can be erased and replaced with another micropattern, while preserving the SC. Moreover, an SC, set by crosslinking of the swellable lamellae, is reset by chemical de-crosslinking and subsequent transient re-crosslinking, enabling the SC reconfigurability of the BCP PC film. A prototype of a high-security reconfigurable dual encryption has been developed, wherein true information is decrypted when holographic passwords are confirmed with full-color visible SC passwords.

Permeable polymersomes from temperature and pH dual stimuli-responsive PVCL-b-PLL block copolymers for enhanced cell internalization and lysosome targeting

A series of dual stimuli-responsive block copolymers comprising temperature-responsive poly(N-vinylcaprolactam) (PVCL) and biodegradable pH-responsive poly(l-lysine) (PLL) of varying chain length were synthesized by a combination of free radical polymerization and ring opening polymerization. The block copolymers formed micelles and vesicles (polymersomes) in response to temperature and pH, respectively, in aqueous solution. The nanoassemblies were characterized by transmission electron microscopy and dynamic light scattering techniques. Encapsulation of both hydrophobic and hydrophilic dyes in the polymersomes was shown. Doxorubicin (DOX) was loaded in the polymersomes and its controlled release in response to the two stimuli, independently and jointly, was studied. The drug was found to be released due to stimuli-induced increased permeability without disassembly of the polymersomes. A significant increase in the cellular uptake of the drug-loaded polymersomes at hyperthermia conditions was demonstrated at 41 °C and release of the drug upon localization in lysosomes was observed. Cellular internalization pathway of the polymersomes was investigated by competitive inhibition assay and a combination of endocytic pathways dominated by caveolae-mediated mechanism was found to be operative.

Preparation of pH-responsive block copolymers for separation of cephalosporin antibiotics by open-tubular capillary electrochromatography

Stimuli-responsive block copolymers have exhibited their feasibility for drug delivery and analysis of biomolecules. However, study of the electrophoretic behavior of antibiotics by open tubular capillary electrochromatography (OT-CEC) based on smart block copolymers coatings is still a substantial challenge. Herein, we reported an OT-CEC protocol for analysis of cephalosporin antibiotics with pH-responsive block copolymers as coatings. By using the reversible addition-fragmentation chain-transfers radical polymerisation technique, the smart poly(styrene-maleic anhydride-acrylic acid) (P(St-MAn-AA)) was synthesized and subsequently chemical bonded onto the inner walls of amino-grafted capillaries. The pH induced changes in the stretch/curl states of P(St-MAn-AA) chains were used to generate an adjustable hydrophobic/hydrophilic interaction and hydrogen bonds between the polymer coatings and the analytes. The OT-CEC performance was evaluated by varying the monomer ratios, polymer coating amounts and layers, buffer concentrations and pH values. Baseline separation of the three-test antibiotics was achieved at pH 8.0. The proposed OT-CEC technique was further applied to the determination of rat serum antibiotics in the metabolic processes. The present work demonstrates an enhancement in antibiotics separation efficiency, and shows a great potential for the preparation of stimuli-responsive block copolymers coatings and in OT-CEC analysis of real samples in living bio-systems.

Perfluorocarbon Nanodroplets for Dual Delivery with Ultrasound/GSH-Responsive Release of Model Drug and Passive Release of Nitric Oxide.

Nitric oxide (NO) plays a critical role as an important signaling molecule for a variety of biological functions, particularly inhibiting cell proliferation or killing target pathogens. To deliver active radical NO gaseous molecule whose half-life is a few seconds in a stable state, the design and development of effective exogenous NO supply nanocarriers are essential. Additionally, the delivery of desired drugs with NO can produce synergistic effects. Herein, we report a new approach that allows for the fabrication of dual ultrasound (US)/glutathione (GSH)-responsive perfluorocarbon (PFC) nanodroplets for the controlled release of model drug and passive release of safely incorporated NO. The approach centers on the synthesis of a disulfide-labeled amphiphilic block copolymer and its use as a GSH-degradable macromolecular emulsifier for oil-in-water emulsification process of PFC. The fabricated PFC nanodroplets are colloidally stable and enable the encapsulation of both NO and model drugs. Encapsulated drug molecules are synergistically released when ultrasound and GSH are presented, while NO molecules are passively but rapidly released. Our preliminary results demonstrate that the approach is versatile and can be extended to not only GSH-responsive but also other stimuli-responsive block copolymers, thereby allowing for the fabrication of broad choices of stimuli-responsive (smart) PFC-nanodroplets in aqueous solution for dual delivery of drug and NO therapeutics.

Stimuli-responsive block copolymers as pH chemosensors by fluorescence emission intensification mechanism

Stimuli-responsive block copolymers containing light-responsive coumarin moieties were synthesized using 7-(2-bromoisobutyryloxy)-4-methylcoumarin as an initiator of atom transfer radical polymerization. The resulted smart block copolymers, poly(7-acryloyloxy 4-methylcoumarin-r-methyl methacrylate)-b-poly(dimethylaminoethyl methacrylate) (P(CMA-r-MMA)-b-PDMAEMA) and poly(7-acryloyloxy 4-methylcoumarin)-b-poly(dimethylaminoethyl methacrylate) (PCMA-b-PDMAEMA), were used for pH detection by aggregation-induced fluorescence emission intensification mechanism. Calculation of hydrophilic fraction of the block copolymers by nuclear magnetic resonance spectroscopy proved micellar structure of self-assembled copolymer chains in aqueous media. Dimerization kinetics of the coumarin moieties in the micellar assemblies was investigated by ultraviolet–visible spectroscopy at different pH values. The resulted aqueous micellar dispersions of the block copolymers with different compositions were utilized for pH detection by using fluorescence spectroscopy. The copolymer containing MMA units as a spacer between coumarin moieties (P(CMA-r-MMA)-b-PDMAEMA) showed higher dimerization kinetics and applicability as a fluorescence chemosensor for detection of pH. By contraction of PDMAEMA blocks at higher pH values and consequent aggregation state of the coumarin moieties in the core, the change of fluorescence intensity was used for fluorescence sensation of pH.

Smart block copolymers as fluorescence chemosensors of copper ions with high detection limit

Stimuli-responsive block copolymers were synthesized to detect copper ions with high limit based on a fluorescence quenching mechanism. For this purpose, poly(7-acryloyloxy 4-methylcoumarin-r-methyl methacrylate)-b-poly(dimethylaminoethyl methacrylate) in three different block ratios was synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization. Successful synthesis of the block copolymers was confirmed by Fourier-transformed infrared and proton nuclear magnetic resonance spectroscopies. Self-assembly of the copolymers in aqueous media resulted in formation of micellar structures, as confirmed by transmission electron microscopy images and also estimated form the hydrophilic fraction of the block copolymers. Micellar size and dispersity were studied by dynamic light scattering in different conditions. In addition, dimerization kinetics of the coumarin molecules in the micellar assemblies were studied by ultraviolet–visible spectroscopy. The sample with higher molar ratio of CMA in the hydrophobic block and shorter length of PDMAEMA in the hydrophilic block showed faster dimerization reaction. The micellar assemblies formed from all the copolymers were used to sense potassium, calcium, and copper cations. All the self-assembled structures showed high sensitivity to detect copper cation, by quenching their fluorescence intensity. The copolymer sample with the highest ratio of PDMAEMA/CMA in the chain structure has the highest detection limit of 0.002 ppm for copper ion.

One-step preparation of double emulsions stabilized with amphiphilic and stimuli-responsive block copolymers and nanoparticles for nutraceuticals and drug delivery

One-step emulsification approaches enable prevention of the loss of emulsion droplets associated with two-step emulsification approaches. Stimuli-responsive amphiphilic block copolymers, emulsifiers, and nanoparticles that are responsive to changes in the temperature, pH, presence of CO 2 , or presence of salts, can eliminate the requirement for two hydrophilic and lipophilic emulsifiers in the emulsion system. The amphiphilic block copolymers prepared from naturally occurring amino acids and proteins enable targeted delivery of drugs and nutraceuticals with high cellular uptake. Likewise, the presence of impurities, such as salts and redox reactions driven by the presence of iodine, can result in spontaneous emulsification and formation of double emulsions. This timely review focuses on the application of double emulsions for delivery of drugs and nutraceuticals and will provide insights to scientists in the pharmaceutical industry or food nutritionists who consider fortification of food products with micronutrients. • One-step preparation of double emulsions can prevent the loss of internal emulsion droplets during processing. • Stabilization of double emulsions with amphiphilic copolymers can prevent the need for two various emulsifiers. • The stimuli-responsive copolymers can enable encapsulation and controlled release of nutraceuticals and drugs. • Hydrophilicity or lipophilicity of block copolymers can be tuned by adjusting the length of blocks and oil composition.

Hypoxia/Temperature/pH Triple Stimuli–Responsive Block Copolymers: Synthesis, Self‐Assembly, and Controlled Drug Release

AbstractThe amphiphilic block copolymer poly(methacrylic acid‐co‐2‐nitroimidazole acrylate)‐b‐poly(2‐(N,N‐dimethylamino)ethyl methacrylate) (P(MAA‐co‐NIMA)‐b‐PDMAEMA) with the hypoxia/temperature/pH triple responsiveness is synthesized by reversible addition‐fragmentation chain transfer polymerization (RAFT), hydrolysis, and 3‐(3‐dimethylaminopropyl)‐1‐ethylcarbodiimide (EDC) reactions, and successfully self‐assembled into micelles. The hypoxia response in vitro is realized, and then the sensitivity of the self‐assembled micelles to the hypoxia condition is studied by controlling the grafting amount of aminated 2‐nitroimidazole. Because 2‐(N,N‐dimethylamino) ethyl methacrylate (DMAEMA) is a typical material sensitive to temperature and pH conditions, the self‐assembled micelles are also responsive to temperature and different acidic/basic conditions. In addition, the cumulative release rate of doxorubicin (DOX) at 42 °C, pH = 6.0, and hypoxic conditions increases significantly, and verifies the synergistic promotion effect of the above stimulations. This intelligent polymer with triple response mechanism improves the controllability and efficiency of drug release, and is expected to be a drug carrier for cancer treatment.

Core-crosslinked, temperature- and pH-responsive micelles: design, physicochemical characterization, and gene delivery application.

Stimuli-responsive block copolymer micelles can provide tailored properties for the efficient delivery of genetic material. In particular, temperature- and pH-responsive materials are of interest, since their physicochemical properties can be easily tailored to meet the requirements for successful gene delivery. Within this study, a stimuli-responsive micelle system for gene delivery was designed based on a diblock copolymer consisting of poly(N,N-diethylacrylamide) (PDEAm) as a temperature-responsive segment combined with poly(aminoethyl acrylamide) (PAEAm) as a pH-responsive, cationic segment. Upon temperature increase, the PDEAm block becomes hydrophobic due to its lower critical solution temperature (LCST), leading to micelle formation. Furthermore, the monomer 2-(pyridin-2-yldisulfanyl)ethyl acrylate (PDSAc) was incorporated into the temperature-responsive PDEAm building block enabling disulfide crosslinking of the formed micelle core to stabilize its structure regardless of temperature and dilution. The cloud points of the PDEAm block and the diblock copolymer were investigated by turbidimetry and fluorescence spectroscopy. The temperature-dependent formation of micelles was analyzed by dynamic light scattering (DLS) and elucidated in detail by an analytical ultracentrifuge (AUC), which provided detailed insights into the solution dynamics between polymers and assembled micelles as a function of temperature. Finally, the micelles were investigated for their applicability as gene delivery vectors by evaluation of cytotoxicity, pDNA binding, and transfection efficiency using HEK293T cells. The investigations showed that core-crosslinking resulted in a 13-fold increase in observed transfection efficiency. Our study presents a comprehensive investigation from polymer synthesis to an in-depth physicochemical characterization and biological application of a crosslinked micelle system including stimuli-responsive behavior.

Dual Stimuli-Responsive Block Copolymers with Adjacent Redox- and Photo-Cleavable Linkages for Smart Drug Delivery.

A novel dual-stimuli cleavable linker containing adjacent UV light-sensitive o-nitrobenzyl ester and GSH-responsive disulfide bonds was first designed and synthesized to increase the responsivity to external stimuli. The functionalized linker was then utilized to prepare a dual-responsive amphiphilic block copolymer using ring-opening polymerization and atom transfer radical polymerization. The copolymer formed a micelle in an aqueous solution and showed dual-stimuli responses including photo-mediated cleavage under UV light irradiation at 365 nm as well as reduction-responsive degradation in the presence of a reducing agent. The micelle was nontoxic against three cell lines and majorly internalized via clathrin-mediated endocytosis. Doxorubicin (Dox) was loaded in the hydrophobic core of the micelle. Enhancement of a cell-killing effect against A549 cells was clearly observed in the Dox-encapsulated micelle when exposed to UV light.

The Importance of Cooperativity in Polymer Blending: Toward Controlling the Thermoresponsive Behavior of Blended Block Copolymer Micelles.

Understanding, predicting, and controlling the self-assembly behavior of stimuli-responsive block copolymers remains a pertinent challenge. As such, the copolymer blending protocol provides an accessible methodology for obtaining a range of intermediate polymeric nanostructures simply by blending two or more block copolymers in the desired molar ratio to target specific stimuli-responsiveness. Herein, thermoresponsive diblock copolymers are blended in various combinations to investigate whether the resultant cloud point temperature can be modulated by simple manipulation of the molar ratio. Thermoresponsive amphiphilic diblock copolymers composed of statistical poly(n-butyl acrylate-co-N,N-dimethylacrylamide) core-forming blocks and four different thermoresponsive corona-forming blocks, namely poly(diethylene glycol monomethyl ether methacrylate) (p(DEGMA)), poly(N-isopropylacrylamide), poly(N,N-diethylacrylamide), and poly(oligo(ethylene glycol) monomethyl ether methacrylate) (p(OEGMA)) are selected for evaluation. Using variable temperature turbidimetry, the thermoresponsive behavior of blended diblock copolymer self-assemblies is assessed and compared to the thermoresponsive behavior of the constituent pure diblock copolymer micelles to determine whether comicellization is achieved and more significantly, whether the two blended corona-forming thermoresponsive blocks exhibit cooperative behavior. Interestingly, blended diblock copolymer micelles composed of p(DEGMA)/p(OEGMA) mixed coronae display cooperative behavior, highlighting the potential of copolymer blending for the preparation of stimuli-responsive nanomaterials in applications such as oil recovery, drug delivery, biosensing, and catalysis.

Length effect of stimuli-responsive block copolymer prodrug filomicelles on drug delivery efficiency

Filomicelles possess some unique properties for improved in vivo drug delivery efficiency relative to commonly used spherical nanocarriers, which have attracted great interests. However, the length effect of the block copolymer prodrug-based filomicelles with a comparable cross-section diameter on the drug delivery efficiency and antitumor efficacy still need to be systematically studied. In this report, we prepare three optimized nanoparticles with a comparable cross-section diameter of ~40 nm, including long filomicelles (LFMs) with the length of ~2.5 μm, short filomicelles (SFMs) with the length of ~180 nm, and spherical micelles (SMs) with a diameter of ~40 nm. All of them are self-assembled from the pH and oxidation dual-responsive block copolymer prodrug, PEG-b-P(CPTKMA-co-PEMA), consisting of poly(ethylene glycol) (PEG) and a copolymerized block of thioketal-linked camptothecin methacrylate (CPTKMA) and 2-(pentamethyleneimino) ethyl methacrylate (PEMA). At pH 6.5, the nanoparticles are positively charged due to the protonation of PPEMA segments. Among them, SFMs are demonstrated to be internalized into cells most efficiently at pH 6.5 due to larger interaction areas with cell membranes relative to SMs. Moreover, SFMs show prolonged blood circulation similar to SMs as well as deepest tumor penetration and best antitumor efficacy among the three nanoparticles. LFMs show worst in vivo performance because their too long structure limits the cellular uptake and tumor accumulation. Therefore, the responsive polymer prodrug filomicelles with an optimized length show great potentials to overcome the physiological barriers and improve the drug delivery efficiency.

Controlled Microfluidic Synthesis of Biological Stimuli-Responsive Polymer Nanoparticles.

Microfluidic flow-directed self-assembly of biological stimuli-responsive block copolymers is demonstrated with dual-location cleavable linkages at the junction between hydrophilic and hydrophobic blocks and on pendant group within the hydrophobic blocks. On-chip self-assembly within a two-phase microfluidic reactor forms various "DualM" polymer nanoparticles (PNPs), including cylinders and multicompartment vesicles, with sizes and morphologies that are tunable with manufacturing flow rate. Complex kinetically trapped intermediates between shear-dependent states provide the most detailed mechanism to date of microfluidic PNP formation in the presence of flow-variable high shear. Glutathione (GSH)-triggered changes in PNP size and internal structure depend strongly on the initial flow-directed size and internal structure. Upon incubation in GSH, flow-directed PNPs with smaller average sizes showed a faster hydrodynamic size increase (attributed to junction cleavage) and those with higher excess Gibbs free energy showed faster inner compartment growth (attributed to pendant cleavage). These results demonstrate that the combination of chemical control of the location of biologically responsive linkages with microfluidic shear processing offers promising routes for tunable "smart" polymeric nanomedicines.

Light- and temperature-responsive micellar carriers prepared by spiropyran-initiated atom transfer polymerization: Investigation of photochromism kinetics, responsivities, and controlled release of doxorubicin

Stimuli-responsive block copolymer assemblies are a significant class of smart materials extensively studied for advanced applications such as drug- and gen-delivery systems. Different types of light- and temperature-responsive polymer assemblies containing photochromic spiropyran chain end groups, temperature-responsive poly (N-isopropylacrylamide) (PNIPAM) block, and hydrophobic poly (methyl methacrylate) (PMMA) block were developed. These amphiphilic block copolymers with the ability of self-assembly to micellar structures were synthesized using spiropyran-initiated atom transfer radical polymerization. Regarding the hydrophilic fraction (0.5<fphilic), the amphiphilic block copolymers were self-assembled to spherical micelles in aqueous media as confirmed by TEM images. The size of these polymer assemblies was changed in response to temperature changes and also UV light (365 nm) irradiation. The results of UV–Vis spectroscopy display that photochromic behavior, the kinetics of spiropyran (SP) to merocyanine (MC) and MC to SP isomerizations were significantly affected by the polarity of the polymer blocks in neighboring of the spiropyran chain end group. The lower critical solution temperature (LCST) of PNIPAM shows a shift from 26.5 to 37.5 °C after isomerization of the SP to MC, as a result of increase of its polarity and water-solubility. The doxorubicin (DOX) release can be controlled by pH, temperature, and light by using of multi-responsive block copolymer micelles as smart drug carriers. The release efficiency was reached to 60–85% at pH 5.3, 80–90% at temperatures of above LCST of PNIPAM (40 °C), and also 90–100% under UV irradiation after 48 h. The results display that stimuli-responsive polymer assemblies based on amphiphilic block copolymers containing spiropyran chain end groups are applicable in smart drug-delivery systems, and offer controlling over drug-release by different triggers, such as light irradiation, pH variation, and temperature changes.

Self-assembly of stimuli-responsive block copolymers in aqueous solutions: an overview

The review reports an aqueous solution behavior of commercially available and easy-to-use polymers, i.e., Pluronics®- and PNIPAM-based block copolymers. Both the polymers are stimuli responsive in nature. The present review covers the different aspects of aggregation behavior of Pluronics®- and PNIPAM-based block copolymeric micelles. Here, a comparison of physical properties such as EO–PO block, CP, CMC and CMT is made. Such physical parameters can be modulated with ease by the presence of external stimuli, viz. electrolytes, organic additives such as alcohols, phenols, amides and acids, different types of surfactants and water-soluble polymers, and also by modification of end groups of Pluronics®. But in this review, our main focus is to study the addition of salts and non-electrolytes on the aggregation behavior of Pluronics®. With the help of above parameters, users can get idea about the stability, partition coefficient, solubilization capacity, etc. In analogy with Pluronics®, PNIPAM is also a thermo-responsive polymer with ~ 32 °C lower critical solution temperature (LCST). However, the LCST is independent of the degree of polymerization, i.e., molecular weight of homopolymer. However, the LCST can be tuned in the presence of external stimulus. PNIPAM-based di-block copolymers form various morphologies in different environments. An inverted morphology by double-hydrophilic-block copolymers is also possible. According to US and British Pharmacopoeia, some of the Pluronics® and PNIPAM are recognized as pharmaceutical excipients. Therefore, they have been extensively used for various pharmaceutical formulations. The other applications of these polymers are tissue engineering, bioseparation devices, active membranes, biosensors, rheological modifier, lithium batteries, etc.

A Simple Route to Hierarchical Rings of Diblock Copolymer Micelles.

A hierarchically assembled necklace composed of amphiphilic diblock copolymer micelles is exquisitely produced by capitalizing on two concurrent self-assembly processes at different scales (i.e., "breath figure" strategy of diblock copolymer micelles solution evaporating in humid air to yield rings at the microscopic scale in conjunction with self-assembly of diblock copolymer micelles within individual ring at the nanometer scale). Intriguingly, hierarchical rings of diblock copolymer micelles comprising gold precursors or fluorescent dyes can also be crafted using this strategy. Upon exposure to hydrophilic block-selective solvent, core-corona inversion of micelles within the microscopic rings occurs. In contrast, such inversion is inhibited when the micelles are impregnated by gold precursors. This simple yet effective strategy for engineering diblock copolymer micelles may be extended to produce hierarchically assembled structures consisting of other functional block copolymers (e.g., stimuli-responsive block copolymer) and nanocrystals (e.g., semiconducting, magnetic, ferroelectric, etc.) with unique catalytic, magnetic, ferroelectric, optical, electronic, and optoelectronic properties.

Stimuli-Responsive Lyotropic Liquid Crystalline Nanosystems with Incorporated Poly(2-Dimethylamino Ethyl Methacrylate)-b-Poly(Lauryl Methacrylate) Amphiphilic Block Copolymer.

There is an emerging need to evolve the conventional lyotropic liquid crystalline nanoparticles to advanced stimuli-responsive, therapeutic nanosystems with upgraded functionality. Towards this effort, typically used stabilizers, such as Pluronics®, can be combined or replaced by smart, stimuli-responsive block copolymers. The aim of this study is to incorporate the stimuli-responsive amphiphilic block copolymer poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) (PDMAEMA-b-PLMA) as a stabilizer in lipidic liquid crystalline nanoparticles, in order to provide steric stabilization and simultaneous stimuli-responsiveness. The physicochemical and morphological characteristics of the prepared nanosystems were investigated by light scattering techniques, cryogenic-transmission electron microscopy (cryo-TEM), X-ray diffraction (XRD) and fluorescence spectroscopy. The PDMAEMA-b-PLMA, either individually or combined with Poloxamer 407, exhibited different modes of stabilization depending on the lipid used. Due to the protonation ability of PDMAEMA blocks in acidic pH, the nanoparticles exhibited high positive charge, as well as pH-responsive charge conversion, which can be exploited towards pharmaceutical applications. The ionic strength, temperature and serum proteins influenced the physicochemical behavior of the nanoparticles, while the polymer concentration differentiated their morphology; their micropolarity and microfluidity were also evaluated. The proposed liquid crystalline nanosystems can be considered as novel and attractive pH-responsive drug and gene delivery nanocarriers due to their polycationic content.

Light-responsive block copolymers with a spiropyran located at the block junction

Block copolymers with a functional group between their blocks are relatively little explored even though this molecular architecture can reduce the aggregation of the functional groups, promote the phase separation in nanophase-separated materials, and has other interesting effects. Spiropyrans are well-known for their ability to switch to their polar merocyanine form in response to light, force and other stimuli. The synthesis of stimuli-responsive AB-type block copolymers with spiropyran moieties located at the junction of the blocks is presented here. A homopolymer is synthesized from a trimethylindolenine-based atom transfer radical polymerization (ATRP) initiator, followed by its modification to a spiropyran end-functionalized polymer. The spiropyran functionalized polymer is then used as a macro-initiator for the synthesis of a second polymer block by ring opening polymerization (ROP). Alternatively, spiropyran homopolymers are conjugated to other preformed polymers by esterification. The resulting block copolymers reversibly switch under UV and white light irradiation over multiple cycles, and a block copolymer reduced the tendency of the merocyanine to aggregate during switching. The stimuli-responsive block copolymer could be useful for a range of applications, e.g. for bioinspired polymersome nanoreactors, or in membranes with switchable permeability.