Star-like Copolymers Research Articles

Toxicity of Water-Soluble D-g-PNIPAM Polymers in a Complex with Chemotherapy Drugs and Mechanism of Their Action In Vitro.

The application of a biocompatible polymer nanocarrier can provide target delivery to tumor tissues, improved pharmacokinetics, controlled drug release, etc. Therefore, the proposed strategy was to use the water-soluble star-like copolymers with a Dextran core and Poly(N-isopropylacrylamide) grafts (D-g-PNIPAM) for conjugation with the widely used chemotherapy drugs in oncology-Cisplatin (Cis-Pt) and Doxorubicin (Dox). The molecular characteristics of the copolymer were received using size-exclusion chromatography. The physicochemical characterization of the D-g-PNIPAM-Cis-Pt (or Dox) nanosystem was conducted using dynamic light scattering and FTIR spectroscopy. Using traditional biochemical methods, a comparative analysis of the enhancement of the cytotoxic effect of free Cis-Pt and Dox in combination with D-g-PNIPAM copolymers was performed in cancer cells of the Lewis lung carcinoma line, which are both sensitive and resistant to Dox; in addition, the mechanism of their action in vitro was evaluated.

Starlike Copolymer Nanoreactors for the Controlled Preparation of Highly Uniform Liquid Metal Nanoparticles

Starlike Copolymer Nanoreactors for the Controlled Preparation of Highly Uniform Liquid Metal Nanoparticles

Molecular mobility and thermal transitions study in renewable PLA-polyols star-like copolymers

The molecular dynamics mapping in poly(lactic acid) (PLA)-based star-like copolymers is performed herein, employing dielectric spectroscopy techniques supplemented by calorimetry and other structure characterization methods. Next to the neat linear PLA, three star-like copolymers, with 3, 4 and 5 branches were synthesized via ring opening polymerization at the presence of, respectively, glycerol, pentaerythritol and sorbitol (initiators). When increasing the branch number, consequently, the overall molar mass drops, from 55 kg/mol (neat PLA) to 17k (PLA@glycerol), 25k (PLA@pentaerythritol), and 14k (PLA@sorbitol) and, thus, the branch length decreases to ∼6k, ∼6k, and ∼3 k g/mol in the stars. The latter leads to faster segmental mobility, documented by the accelerated α relaxation and the drop in the calorimetric and dielectric glass transition temperatures. Simultaneously, the cooperativity (chains’ fragility) drops. Together these results suggest possibly the increase in free volume, a factor that can potentially favour the physical biodegradability. Next to the segmental dynamics, the local beta relaxation is recorded to have a mild dependence on the type of star (mainly decelerates), while the rare case of Normal Mode relaxation is recorded here only in the stars, providing additional support for the quite short branches. The overall data suggest the co-implementation of two antagonistic effects on mobility, i.e., the chain length changes in parallel to the constraints imposed by the star-like structure. Moreover, the in general low crystallizability of linear PLA further drops in the stars in terms of both suppressed crystalline fraction and nucleation, as well as lower quality of crystals. The materials exhibit single thermal transitions, indicating a homogeneous character, whereas a variety of semicrystalline morphologies can be achieved via both the composition and the thermal treatment. This provides a tool for tuning various properties and, consequently, the manipulation of the macroscopic performance.

Self-Assembled Copolymeric Nanowires as a New Class of 3D Scaffold for Stem Cells Growth and Proliferation

Stem cell therapy has emerged as the most vibrant area of research, due to the capacity of stem cells for self-renewal and differentiation into different types of cell lines upon their culture. But lately, scientists become increasingly aware of the limitations of conventional 2D culture and stem cell culture media, due to several key drawbacks associated with this model, such as immune response upon transplantation, animal pathogen contamination, and complication, during developmental studies due to undefined factors in the cultural media. In this study, an attempt has been made to develop a new type of polymeric 3D scaffold based on the self-assembly of a star-like amphiphilic copolymer of poly(caprolactone)–poly(ethylene oxide) unit into nanowires (nanofibers), that have a scale similar to the native extracellular matrix and are capable of mimicking the extracellular microenvironment where the functional properties of stem cells can be observed and manipulated. The obtained data showed that polymeric-based nanofibers can be used as a 3D scaffold for mouse embryonic stem cells (mESCs) growth without losing their stem cell phenotype. The results obtained suggest that the polymeric 3D scaffolds (nanofibers) not only support stem cells’ growth and proliferation but also preserve the mESC pluripotency.

Silver Nanocrystal Array with Precise Control via Star-like Copolymer Nanoreactors.

Silver nanocrystal arrays had attracted much attention due to the unique plasmonic effect of their ordered nanostructure and the synergy among adjacent nanocrystals. Conventional preparation methods had several limitations, such as high cost, harsh preparation conditions, and complicated influencing factors, which could not be employed to fabricate the nanocrystal arrays in highly controlled fashion. To solve these issues, we reported ordered arrays of different Ag nanocrystals with precise control prepared by utilizing amphiphilic star-like poly(4-vinylpyridine)-block-polystyrene diblock copolymers as nanoreactors synthesized by sequential atom transfer radical polymerization. Moreover, this unimolecular nanoreactor method based on star-like copolymers with stable and predesigned nanostructures was proved to be a universal approach to prepare other nanocrystal arrays. This strategy had low cost, simple process flow, wide applicability, and structural stability that could fabricate nanocrystal array with precise control and continuously prepare more complex nanostructure units in a large scale to meet different functions and applications.

Efficient Retention and Alpha Spectroscopy of Actinides from Aqueous Solutions Using a Combination of Water-Soluble Star-like Polymers and Ultrafiltration Membranes.

We explored two approaches to recover uranium and plutonium from aqueous solutions at pH 4 and pH 7 using water-soluble star-like polyacrylamide polymers with a dextran core. In the first approach, a solution comprising a neutral or ionomer polymer was mixed with a radionuclide solution to form polymer–metal complexes that were then retained by ultrafiltration (UF) membranes under applied pressure. The same polymers were first deposited on the membrane in the second approach using pressure-driven flow. The applied polymers had an overall diameter of gyration of 120 nm, which exceeded the nominal diameter of the UF membrane pores. The polymers showed a high affinity to uranyl but could also be used to extract Pu from neutral or near-neutral pH solutions. Direct-flow single-step filtration and alpha spectrometry demonstrated that the UF membranes containing star-like copolymers could recover 99% of U and up to 60% of Pu from deionized water after filtering 15 mL solutions containing 25 ppm and 33 ppb of the actinides, correspondingly. The sorption capacity of the polymers for uranium could be measured as 1mg U per mg of the polymer after six subsequent filtration steps. Alpha spectroscopy of the deposited actinides revealed peculiarities of the structural organization of polymers and their complexes with U or Pu, depending on the approach. Though both approaches were efficient, the second approach (deposition of the polymer on the membrane followed by filtration) has an additional advantage of protecting the membrane pores from capillary collapse by filling them with the polymer chains. Therefore, these polymer-modified membranes could be used either in continuous or multi-step filtration process with drying after each step without deterioration of their sorption characteristics.

Maltotriose-based star polymers as self-healing materials

Self-healing polymers with complementary functional groups can spontaneously repair mechanical damage. We developed star-like block copolymers from a naturally-derived maltotriose core with acrylate arms consisting of soft poly(n-butyl acrylate) (PnBA) and hard poly(tert-butyl acrylate) (PtBA) segments, exhibiting self-repair behavior. A facile and efficient two-step synthesis involving a “core-first” approach employed a simplified electrochemically mediated ATRP (seATRP) with only 25 ppm of a copper catalyst. Precise control was maintained during the polymerization of both acrylates, yielding soft and hard segments. Macromolecules with maltotriose core and polymer arms composed of PnBA homopolymer or poly(n-butyl acrylate)-block-poly(tert-butyl acrylate) (PnBA-b-PtBA) block copolymer had a narrow molecular weight distribution (Mw/Mn = 1.13 and 1.17, respectively). Thermomechanical properties of maltotriose-based star-like copolymers and their linear counterpart were studied by thermogravimetry (TGA), differential scanning calorimetry (DCS) and tensile analysis. The star-like polymers exhibited self-healing behavior. A complete repair of the damaged material occurred after 30 min without external intervention under ambient conditions.

Constructing a Rigid-and-Flexible Twin-Stage Gradient Interphase through Starlike Copolymer Coating on Carbon Fibers: A Route for Enhancing Interfacial Properties of Composites.

A rigid-and-flexible interphase was established by a starlike copolymer (Pc-PGMA/Pc) consisting of one tetraaminophthalocyanine (TAPc) core with four TAPc-difunctionalized poly(glycidyl methacrylate) (PGMA) arms through the surface modification of carbon fibers (CFs) and compared with various interphases constructed by TAPc and TAPc-connected PGMA (Pc-PGMA). The increase in the content of N-C═O showed that PGMA/Pc branches were successfully attached onto the CF-(Pc-PGMA/Pc) surface, exhibiting concavo-convex microstructures with the highest roughness. Through adhesive force spectroscopy by atomic force microscopy (AFM) with peak force quantitative nanomechanical mapping (PF-QNM) mode and visualization of the relative distribution of TAPc/PGMA via a Raman spectrometer, a rigid interphase with highly cross-linked TAPc and a flexible layer from PGMA arms as the soft segment were separately detected in CF-TAPc/EP and CF-(Pc-PGMA)/EP composites. The rigid-and-flexible interphase in the CF-(Pc-PGMA/Pc)/EP composite provided excellent stress-transfer capability by the rigid inner modulus intermediate layer and energy absorption efficiency from the flexible outer layer, which contributed to 64.6 and 61.8% increment of transverse fiber bundle test (TFBT) strength, and 33.8 and 40.6% enhancement in interfacial shear strength (IFSS) in comparison with those of CF-TAPc/EP and CF-(Pc-PGMA)/EP composites. Accordingly, schematic models of the interphase reinforcing mechanism were proposed. The interfacial failures in CF-TAPc/EP and CF-(Pc-PGMA)/EP composites were derived from the rigid interphase without effective relaxation of interfacial stress and soft interphase with excessive fiber-matrix interface slippage, respectively. The cohesive failure in the CF-(Pc-PGMA/Pc)/EP composite was attributed to the crack deflection through the balance of the modulus and deformability from the twin-stage gradient intermediate layer.

A New Water-Soluble Thermosensitive Star-Like Copolymer as a Promising Carrier of the Chemotherapeutic Drug Doxorubicin.

A new water-soluble thermosensitive star-like copolymer, dextran-graft-poly-N-iso-propilacrylamide (D-g-PNIPAM), was created and characterized by various techniques (size-exclusion chromatography, differential scanning calorimetry, Fourier-transform infrared (FTIR) spectroscopy, and dynamic light scattering (DLS) spectroscopy). The viability of cancer cell lines (human transformed cervix epithelial cells, HeLa) as a model for cancer cells was studied using MTT and Live/Dead assays after incubation with a D-g-PNIPAM copolymer as a carrier for the drug doxorubicin (Dox) as well as a D-g-PNIPAM + Dox mixture as a function of the concentration. FTIR spectroscopy clearly indicated the complex formation of Dox with the D-g-PNIPAM copolymer. The size distribution of particles in Hank’s solution was determined by the DLS technique at different temperatures. The in vitro uptake of the studied D-g-PNIPAM + Dox nanoparticles into cancer cells was demonstrated by confocal laser scanning microscopy. It was found that D-g-PNIPAM + Dox nanoparticles in contrast to Dox alone showed higher toxicity toward cancer cells. All of the aforementioned facts indicate a possibility of further preclinical studies of the water-soluble D-g-PNIPAM particles’ behavior in animal tumor models in vivo as promising carriers of anticancer agents.

Tailoring electrocatalytic activity of in situ crafted perovskite oxide nanocrystals via size and dopant control

Perovskite oxides (ABO3) have been widely recognized as a class of promising noble-metal-free electrocatalysts due to their unique compositional flexibility and structural stability. Surprisingly, investigation into their size-dependent electrocatalytic properties, in particular barium titanate (BaTiO3), has been comparatively few and limited in scope. Herein, we report the scrutiny of size- and dopant-dependent oxygen reduction reaction (ORR) activities of an array of judiciously designed pristine BaTiO3 and doped BaTiO3 (i.e., La- and Co-doped) nanoparticles (NPs). Specifically, a robust nanoreactor strategy, based on amphiphilic star-like diblock copolymers, is employed to synthesize a set of hydrophobic polymer-ligated uniform BaTiO3 NPs of different sizes (≤20 nm) and controlled compositions. Quite intriguingly, the ORR activities are found to progressively decrease with the increasing size of BaTiO3 NPs. Notably, La- and Co-doped BaTiO3 NPs display markedly improved ORR performance over the pristine counterpart. This can be attributed to the reduced limiting barrier imposed by the formation of -OOH species during ORR due to enhanced adsorption energy of intermediates and the possibly increased conductivity as a result of change in the electronic states as revealed by our density functional theory-based first-principles calculations. Going beyond BaTiO3 NPs, a variety of other ABO3 NPs with tunable sizes and compositions may be readily accessible by exploiting our amphiphilic star-like diblock copolymer nanoreactor strategy. They could in turn provide a unique platform for both fundamental and practical studies on a suite of physical properties (dielectric, piezoelectric, electrostrictive, catalytic, etc.) contingent upon their dimensions and compositions.

Fluorescent turn-on carbon dot-cored pseudo unimolecular prodrug micelles for tumor-specific dual-triggered drug delivery

Polymer prodrugs have attracted intense attention in tumor chemotherapy in the form of nanoparticles, nanogels or micelles. However, it is still a challenge to control their particle size and stability. Here, carbon dot-cored star-like copolymer hybrid prodrug (CD-PMHyDOX-ssPEG) has been designed for the tumor-specific fluorescent turn-on and pH/reduction dual-triggered drug delivery. The fluorescence of CDs was almost completely quenched after the surface modification and drug conjugation via both static and dynamic quenching effects. It could easily self-assemble into pseudo unimolecular prodrug micelles in aqueous system with CDs as fluorescent off-on core, acid-labile polymer prodrug block as shell and reduction-triggered detached PEG block as corona, possessing excellent tumor-specific pH and reduction dual-triggered drug release performance. Furthermore, the fluorescence of CDs could be partially recovered after the drug release because of the relief of the dynamic quenching during the drug release.

Unconventional Approach to Fabricating a TiO2 Nanoring with Precise Dimension Control Based on Starlike Polymeric Nanoreactors.

The past few years witnessed the rapid development of bottom-up synthesis strategies for preparing various nanostructures (i.e., nanoparticles, nanorods, nanowires, etc.) with distinct morphology-dependent properties. In this study, we reported a facile and efficient synthesis method for preparing anatase titanium dioxide (TiO2) nanorings based on multiarm, starlike amphiphilic polystyrene-b-poly(acrylic acid) (PS-b-PAA) diblock copolymers as nanoreactors which were prepared via a sequential atom-transfer radical polymerization (ATRP) technique followed by the conversion of polystyrene-b-poly(tert-butyl acrylate) (PS-b-PtBA) to PS-b-PAA. The outer PAA block of nanoreactors possessed carboxylic acid groups which could coordinate with a titanium precursor followed by high-temperature calcination to form crystalline TiO2 nanorings. The living nature of ATRP enabled the precise preparation of starlike diblock copolymer nanoreactors with a controlled length of each block (i.e., PtBA and PS), thereby tailoring the inner diameter and wall thickness of the resulting TiO2 nanorings, which were inaccessible to conventional routes.

Spectroscopic Investigation of Chlorin-Based Photosensitizers in Polymer Matrix

Chlorin e6 and its derivatives are the basis of a number of drugs used in medicine in the treatment of various diseases, including cancer, by photodynamic therapy. Nonpolar derivatives of Chlorin e6—dimethyl ether of Chlorin e6 (DME Ce6) and trimethyl ether of Chlorin e6 (TME Ce6)—are actively studied for application during photodynamic therapy. In this work, based on the electron optical absorption spectra, the interaction of photosensitizer molecules with branched star-like copolymer dextran-graft-polyacrylamide in anionic form was investigated and the possibility of using the latter as a carrier for drug delivery to tumor cells was suggested.

Operando unraveling photothermal-promoted dynamic active-sites generation in NiFe2O4 for markedly enhanced oxygen evolution

The ability to develop highly active and low-cost electrocatalysts represents an important endeavor toward accelerating sluggish water-oxidation kinetics. Herein, we report the implementation and unraveling of the photothermal effect of spinel nanoparticles (NPs) on promoting dynamic active-sites generation to markedly enhance their oxygen evolution reaction (OER) activity via an integrated operando Raman and density functional theory (DFT) study. Specifically, NiFe2O4 (NFO) NPs are first synthesized by capitalizing on amphiphilic star-like diblock copolymers as nanoreactors. Upon the near-infrared light irradiation, the photothermal heating of the NFO-based electrode progressively raises the temperature, accompanied by a marked decrease of overpotential. Accordingly, only an overpotential of 309 mV is required to yield a high current density of 100 mA cm-2, greatly lower than recently reported earth-abundant electrocatalysts. More importantly, the photothermal effect of NFO NPs facilitates surface reconstruction into high-active oxyhydroxides at lower potential (1.36 V) under OER conditions, as revealed by operando Raman spectroelectrochemistry. The DFT calculation corroborates that these reconstructed (Ni,Fe)oxyhydroxides are electrocatalytically active sites as the kinetics barrier is largely reduced over pure NFO without surface reconstruction. Given the diversity of materials (metal oxides, sulfides, phosphides, etc.) possessing the photo-to-thermal conversion, this effect may thus provide a unique and robust platform to boost highly active surface species in nanomaterials for a fundamental understanding of enhanced performance that may underpin future advances in electrocatalysis, photocatalysis, solar-energy conversion, and renewable-energy production.

Redox and pH dual sensitive folate-modified star-like amphiphilic copolymer based on castor oil for controlled doxorubicin delivery

To overcome the problems associated with the use of doxorubicin (DOX), such as low solubility, high toxicity, and side effects, a redox and pH-sensitive drug delivery system based on a star-like copolymer of folate-modified poly (ethylene glycol) (PEG) and biodegradable castor oil was developed. Redox-sensitive disulfide linkage and pH-sensitive imine linkage were incorporated in the backbone of the star-like copolymer, which self-assembled into stable micelles with small particle size (91.67 nm), narrow size distribution, and low CMC value (2.7 mg/L). The disassembly behaviors of the micelles when exposed to endolysosomal pH of 5.5 and a high concentration of GSH were evaluated by scanning electron microscope from the changes of micellar morphology.The micelles were used to load DOX into the hydrophobic core. Drug loading capacity (DLC) and drug loading efficiency (DLE) were calculated to be 15.93% and 96.13%, respectively. In vitro release studies showed that DOX release from micelles followed a redox and pH-triggered manner. The introduction of dual trigger further expedited DOX release.In vitro cytotoxicity of the copolymer against HDF cells was investigated. The star-like copolymer showed no toxicity. While the DOX-loaded micelles suggested enhanced cytotoxicity against HeLa cells. These results indicated that these redox and pH-sensitive micelles have the potential as a nanocarrier for DOX and other hydrophobic anti-cancer drugs.

Structure-to-Efficacy Relationship of HPMA-Based Nanomedicines: The Tumor Spheroid Penetration Study.

Nanomedicines are a novel class of therapeutics that benefit from the nano dimensions of the drug carrier. These nanosystems are highly advantageous mainly within cancer treatment due to their enhanced tumor accumulation. Monolayer tumor cells frequently used in routine preclinical assessment of nanotherapeutics do not have a spatial structural architecture that allows the investigation of the penetration of nanomedicines to predict their behavior in real tumor tissue. Therefore, tumor spheroids from colon carcinoma C26 cells and glioblastoma U87-MG cells were used as 3D in vitro models to analyze the effect of the inner structure, hydrodynamic size, dispersity, and biodegradability of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based nanomedicines carrying anticancer drug pirarubicin (THP) on the penetration within spheroids. While almost identical penetration through spheroids of linear and star-like copolymers and also their conjugates with THP was observed, THP penetration after nanomedicines application was considerably deeper than for the free THP, thus proving the benefit of polymer carriers. The cytotoxicity of THP-polymer nanomedicines against tumor cell spheroids was almost identical as for the free THP, whereas the 2D cell cytotoxicity of these nanomedicines is usually lower. The nanomedicines thus proved the enhanced efficacy within the more realistic 3D tumor cell spheroid system.

Silsesquioxane-cored miktoarm copolymer amphiphiles for fabrication of oxidation-responsive silica-encapsulated polysulfide microspheres

The configuration and amphipathicity of polymer templates are crucial in fabrication of hybrid microspheres via the self-assembling process. Here, a new star-like silsesquioxane-cored miktoarm copolymer (M−T8−P) with desired amphiphilicity was synthesized and sufficiently characterized by various methods. The hybrid amphipathic architectures endowed M−T8−P an attractive capability of stable encapsulation for oxidation-reponsive polysulfides (PSL) synthesized from sulfur and monoterpenes, and facilitated the formation of stable M−T8−P/PSL complex micelles, which further templated the construction of oxidation-active silica microspheres with micrometer dimensions through a simple one-pot sol–gel route. With the increasing of PSL/M−T8−P feed ratio, the size of microspheres and the content of PSL in the resulting microsphere were increased due to PSL droplets providing a soft-template for silica particles to build larger-sized silica microspheres with PSL cores, but the regularity of microspheres was decreased. The increased content of PSL and oxidation treatment could significantly enhanced adsorption capacity of hybrid microsphere for palladium (Ⅱ). On the basis of these promising results, the hybrid copolymer and microspheres might find the applications in water treatment and environmental protection.

Synthesis and characterization of CdS nanoparticles grown in the star-like copolymer

Cadmium sulfide nanoparticles were synthesized in situ in polymer matrix Dextran-g-Polyacrylamide at several pH values. In the present work, it is reported the effect of concentration and pH value on Cadmium sulfide nanoparticle size. The CdS sols were characterized using the Dynamic light scattering, UV–Visible spectroscopy, and Transmission electron microscopy. The absorption spectra of synthesized CdS nanoparticles revealed the blue shift in excitonic transitions with respect to CdS bulk material, clearly confirming the formation of nanoparticles. The decreasing of the pH value caused the formation of larger particles and in general more stable CdS sols.

Synthesis of Amphiphilic and Double Hydrophilic Star-like Block Copolymers and the Dual pH-Responsiveness of Unimolecular Micelle

A series of amphiphilic star-like triblock copolymers with well-defined molecular architectures, molecular weight, and narrow polydispersity were successfully synthesized by sequential atom transfe...

Experimental Approach to the Creation of Efficient Multicomponent Nanocomposites for Antitumor Therapy

Water-soluble polymers with special characteristics can be used as carriers in which the active ingredients are entrapped, encapsulated, adsorbed, or chemically attached. The understanding of the processes occurring during the formation of multicomponent nanosystems is the urgent task for the synthesis of antitumor nanocomposites. Gold nanoparticles (AuNPs), photosensitizer Chlorine e6 (Ce6), and Doxorubicin (Dox) are currently used for the photodynamic therapy and chemotherapy. We have been focused on the study of three-component nanosystems Polymer/AuNPs/Ce6, and four-component nanosystems Polymer/AuNPs/Ce6/Dox at physiological temperatures (37 ∘C). The star-like copolymer with Dextran core and grafted Polyacrylamide chains in nonionic and anionic forms are used as a matrix for the synthesis of nanocomposites. The nanosystems are characterized by the dynamic light scattering and transmission electron microscopy. The increasing of the aggregation processes for the four-component nanosystem Polymer/AuNPs/Ce6/Dox in comparison with the three-component one Polymer/AuNPs/Ce6 is registered. These nanosystems are tested in vitro against the subline of breast carcinoma MCF-7/S – sensitive to cytostatics. It is demonstrated that the increase of the aggregation process occurring in four-component systems leads to the loss of the antitumor activity of multicomponent drugs.