Influence of DNA Type on the Physicochemical and Biological Properties of Polyplexes Based on Star Polymers Bearing Different Amino Functionalities.

The interactions of two star polymers based on poly (2-(dimethylamino)ethyl methacrylate) with different types of nucleic acids are investigated. The star polymers differ only in their functionality to bear protonable amino or permanently charged quaternary ammonium groups, while DNAs of different molar masses, lengths and topologies are used. The main physicochemical parameters of the resulting polyplexes are determined. The influence of the polymer' functionality and length and topology of the DNA on the structure and properties of the polyelectrolyte complexes is established. The quaternized polymer is characterized by a high binding affinity to DNA and formed strongly positively charged, compact and tight polyplexes. The parent, non-quaternized polymer exhibits an enhanced buffering capacity and weakened polymer/DNA interactions, particularly upon the addition of NaCl, resulting in the formation of less compact and tight polyplexes. The cytotoxic evaluation of the systems indicates that they are sparing with respect to the cell lines studied including osteosarcoma, osteoblast and human adipose-derived mesenchymal stem cells and exhibit good biocompatibility. Transfection experiments reveal that the non-quaternized polymer is effective at transferring DNA into cells, which is attributed to its high buffering capacity, facilitating the endo-lysosomal escape of the polyplex, the loose structure of the latter one and weakened polymer/DNA interactions, benefitting the DNA release.

Solvent-Free Templated Synthesis of Core-Crosslinked Star-Shaped Polymers in Supramolecular Body-Centered Cubic Phase.

This study reports the exploration of a solvent-free supramolecular templated synthesis strategy toward highly core-cross-linked star-shaped polymers (CSPs). To achieve this, a kind of cross-linkable giant surfactant, based on a functionalized polyhedral oligomeric silsesquioxanes (POSS) head tethered with a diblock copolymer tail containing reactive benzocyclobutene groups, is designed and prepared. By varying the volume fraction of linear block copolymer tail, these giant surfactants can self-assemble into a body-centered cubic (BCC) structure in bulk, in which the supramolecular spheres are composed of a core of POSS cages, a middle shell of crosslinkable poly(4-vinylbenzocyclobutene) (PBCB) blocks, and a corona of inert polystyrene (PS) blocks. The solvent-free thermally induced cross-linking reaction of the benzocyclobutene groups can be finished in 5 min upon heating, resulting in well-defined polymeric spheres with over 90 linear chains surrounding the cross-linked cores. The outer PS blocks serve as the protection corona to ensure that cross-linking of giant surfactants occurs in each supramolecular spherical domain. Given the modular design and diversity of the POSS-based giant surfactants, it is believed that the strategy may enable access to a wide range of CSPs.

A Facile Approach to Produce Star Polymers Based on Coordination Polymerization.

Many efforts have been devoted to preparing star polymers. Research into coordination polymerization, the most powerful stereoselective process to endow polymers with superb properties, lags far behind those achieved by radical polymerization and ionic polymerization. Herein, we propose a facile strategy to prepare star polymers with regular arms based on coordination polymerization via an insertion reaction between the carbon-heteroatom unsaturated bond and the metal-alkyl species. Terminating a living cis-1,4-selective isoprene polymerization by using isocyanate as cross-linker (CL), a star polyisoprene with low polydispersity was obtained in high yield (91.8 %). A kinetic study showed the star polymer was formed via a step-growth procedure. The types of CL and the ratio of [CL]0 : [Cat.]0 are key factors to determine the arm number and the yield of star polymer. Finally, synthetic IR rubber with a green strength up to 1.99 MPa superior to natural rubber (1.43 MPa) was prepared for the first time.

Self-Organization in Dilute Aqueous Solutions of Thermoresponsive Star-Shaped Six-Arm Poly-2-Alkyl-2-Oxazines and Poly-2-Alkyl-2-Oxazolines.

The behavior of star-shaped six-arm poly-2-alkyl-2-oxazines and poly-2-alkyl-2-oxazolines in aqueous solutions on heating was studied by light scattering, turbidimetry and microcalorimetry. The core of stars was hexaaza [26] orthoparacyclophane and the arms were poly-2-ethyl-2-oxazine, poly-2-isopropyl-2-oxazine, poly-2-ethyl-2-oxazoline, and poly-2-isopropyl-2-oxazoline. The arm structure affects the properties of polymers already at low temperatures. Molecules and aggregates were present in solutions of poly-2-alkyl-2-oxazines, while aggregates of two types were observed in the case of poly-2-alkyl-2-oxazolines. On heating below the phase separation temperature, the characteristics of the investigated solutions did not depend practically on temperature. An increase in the dehydration degree of poly-2-alkyl-2-oxazines and poly-2-alkyl-2-oxazolines led to the formation of intermolecular hydrogen bonds, and aggregation was the dominant process near the phase separation temperature. It was shown that the characteristics of the phase transition in solutions of the studied polymer stars are determined primarily by the arm structure, while the influence of the molar mass is not so significant. In comparison with literature data, the role of the hydrophobic core structure in the formation of the properties of star-shaped polymers was analyzed.

Fabrication of Pore-Selective Metal-Nanoparticle-Functionalized Honeycomb Films via the Breath Figure Accompanied by In Situ Reduction.

Honeycomb films pore-filled with metal (Au, Ag, and Cu) nanoparticles were successfully prepared by combining the breath figure method and an in situ reduction reaction. First, a polyhedral oligomeric silsesquioxane (POSS)-based star-shaped polymer solution containing metal salt was cast under humid conditions for the formation of honeycomb films pore-filled with metal salt through the breath figure method. The morphology of the honeycomb films was mainly affected by the polymer molecular structure and the metal salt. Interestingly, the promoting effect of the metal salt in the breath figure process was also observed. Then, honeycomb films pore-filled with metal nanoparticles were obtained by in situ reduction of the honeycomb films pore-filled with metal salt using NaBH4. Notably, the metal nanoparticles can be selectively functionalized in the pores or on the surface of the honeycomb films by controlling the concentration of the NaBH4. Metal-nanoparticle-functionalized honeycomb films can prospectively be used in catalysis, flexible electrodes, surface-enhanced Raman spectroscopy (SERS), and wettability patterned surfaces.

A Simple and Versatile Method for the Construction of Nearly Ideal Polymer Networks.

Polymer networks usually contain numerous inhomogeneities that deteriorate their physical properties and should be eliminated to create reliable, high-performance materials. A simple method is introduced for the production of nearly ideal networks from various vinyl polymers through controlled polymerization and subsequent crosslinking. Monodisperse star polymers with bromide end groups were synthesized by atom-transfer radical polymerization and end-linked with dithiol linkers using thiol-bromide chemistry. This simple procedure formed nearly ideal polymer networks, as revealed from elasticity of the formed gel and model conjugation reactions involving linear polymers. The versatility of this method was demonstrated by preparing networks of common vinyl polymers, including polyacrylates, polymethacrylate, and polystyrene. This method can be used to prepare multiple functional nearly ideal gels and elastomers and to explore fundamental aspects of polymer networks.

Folate-Targeted Anticancer Drug Delivery via a Combination Strategy of a Micelle Complex and Reducible Conjugation.

Conjugation of various active targeting ligands to the surface of nanocarriers to realize specific recognition by the corresponding receptors localized on the membrane of the cancer cells has provided a powerful means toward enhanced cancer therapy. Folic acid (FA) is one of the most used targeting ligands due to the overexpressed FA receptors in many cancer cell lines. However, conjugation of hydrophobic FA to the surface of nanocarriers usually alters the hydrophilic/hydrophobic balance of the stabilized nanoparticles, leading to their thermodynamic instability and subsequent formation of aggregates, which apparently compromises the in vivo long circulation and minimized side effects of nanocarriers. The currently leading strategy to overcome this issue is to incorporate a protecting hydrophilic stealth that can be deshielded to expose the targeting ligand at the desired tumor site, which generally involves multistep chemical modifications, conjugations, and purifications. To develop a simple alternative toward FA-mediated enhanced anticancer drug delivery, a combination strategy of micelle complex and reducible conjugation was reported in this study. FA was first conjugated to the terminus of the hydrophilic block of a reduction-sensitive miktoarm star-shaped amphiphilic copolymer, PCL3-SS-POEGMA1, with the previously optimized star structure by click coupling via a reducible disulfide link. The resulting PCL3-SS-POEGMA1-SS-FA was further mixed with the parent PCL3-SS-POEGMA1 to afford a micelle complex with both reducibly conjugated and relatively low amount of FA-targeting ligands toward excellent FA-mediated targeted drug delivery without compromised salt stability in vitro and in vivo. Therefore, the combined strategy developed herein provides a simple and powerful means to promote FA-mediated anticancer drug delivery.

Comprehensive branching analysis of star-shaped polystyrenes using a liquid chromatography-based approach.

The comprehensive branching analysis of complex polymers is still a challenge in advanced polymer analysis. Average branching information (average number and length of branches) can be obtained by spectroscopic methods, mainly NMR spectroscopy. The determination of the branching distribution, i.e., the concentration of macromolecules with a given number of branches, however, requires fractionation. Typically, size exclusion chromatography is used that separates the complex mixture with regard to molecular size in solution and not strictly with regard to the number of branches. In the present approach, model star-shaped polystyrenes were synthesized with a pre-determined architecture to give theoretical three-arm, four-arm, and six-arm structures. The branched samples were compared with a linear analogue of comparable molar mass known not to contain branching. Triple detector size exclusion chromatography with refractive index, multiangle light scattering, and online viscometer detection was used to determine absolute molar masses, radii of gyration, and branching distributions of the star-shaped polymers. 1H-NMR was used to calculate the average functionality and a reasonable agreement between the results of the two methods was obtained. Thermal gradient interaction chromatography and solvent gradient interaction chromatography were employed to separate the complex reaction products according to chemical composition (number of branches) and to resolve by-products. The separation capabilities of the two chromatographic techniques were compared and evaluated. Comprehensive two-dimensional liquid chromatography was used to separate the polydisperse star-shaped polystyrenes with regard to both branching and molar mass. Graphical abstract.

Precise Synthesis of PS-PLA Janus Star-Like Copolymer.

In this work, an efficient strategy is designed for the precise synthesis of novel Janus star-like copolymer (polystyrene)8 -b-(poly(l-lactide))8 , (PLLA)8 -b-(PS)8 , consisting of two types of chemically distinct polymer arms, PS and PLLA, in an asymmetric structure. During the synthesis, PLLA hemisphere carrying protected hydroxyl groups at the focal point was first synthesized via a combined reactions of esterification, light-induced "Click" chemistry, and ring opening polymerization (ROP) using a specially designed dendron as initiator. After removing the protecting moiety, the terminal hydroxyl groups on the dendron segment is increased fourfold and further modified into bromopropionate-based macroinitiator through a two-step end group transformation reaction, followed by atom transfer radical polymerization (ATRP) of styrene to obtain the desired (PLLA)8 -b-(PS)8 Janus star-like copolymer. The versatility and efficiency of the designed synthetic strategy are demonstrated by the well-defined molecular characteristics and high yields of the targeted product. In addition to the controlled degradation behavior of the PLLA segments, the remaining bromide groups located at the distal end of PS arms could allow for further fabrication of diverse building blocks through consecutive ATRP of various monomers. This work signifies the first time for facile and precise synthesis of Janus star-like copolymer with unique biphasic structure and function control.

A star-shaped molecularly imprinted polymer derived from polyhedral oligomeric silsesquioxanes with improved site accessibility and capacity for enantiomeric separation via capillary electrochromatography.

A star-shaped molecularly imprinted coating was prepared starting from octavinyl-modified polyhedral oligomeric silsesquioxanes (Ov-POSS). It possesses a relatively open structure and has good site accessibility and a larger capacity even at lower cross-linking. The imprinted coating was prepared from S-amlodipine (S-AML) as the template and analyte, Ov-POSS as the cross-linker, and methacrylic acid as the functional monomer. The preparation and chromatographic parameters were optimized, including ratio of template to functional monomer, apparent cross-linking degree, pH value, ACN content and salt concentration in the mobile phase. The best resolution in enantiomer separation by means of capillary electrochromatography reaches a value of 33. A good recognition ability (α = 2.60) was obtained and the column efficiency for S-AML was 54,000 plates m-1. The use of Ov-POSS as a cross-linker significantly improves the column capacity and thus the detection sensitivity. The results show that Ov-POSS is an effective cross-linker for the preparation of imprinted polymers with good accessibility and large capacity. Graphical abstract Schematic presentation of the preparation of star-shaped imprinted polymer using octavinyl-modified polyhedral oligomeric silsesquioxanes (Ov-POSS) and by using methacrylic acid (MAA) as functional monomer. The best enantiometric resolution (33) for amlodipine (AML) can be achieved in capillary chromatography (CEC).

Star-shaped poly(oligoethylene glycol) copolymer-based gels: Thermo-responsive behaviour and bioapplicability for risedronate intranasal delivery.

The aim of this work was to obtain an intranasal delivery system with improved mechanical and mucoadhesive properties that could provide prolonged retention time for the delivery of risedronate (RS). For this, novel in situ forming gels comprising thermo-responsive star-shaped polymers, utilizing either polyethylene glycol methyl ether (PEGMA-ME 188, Mn 188) or polyethylene glycol ethyl ether (PEGMA-EE 246, Mn 246), with polyethylene glycol methyl ether (PEGMA-ME 475, Mn 475), were synthesized and characterized. RS was trapped in the selected gel-forming solutions at a concentration of 0.2% w/v. The pH, rheological properties, in vitro drug release, ex vivo permeation as well as mucoadhesion were also examined. MTT assays were conducted to verify nasal tolerability of the developed formulations. Initial in vivo studies were carried out to evaluate anti-osteoporotic activity in a glucocorticoid induced osteoporosis model in rats. The results showed successful development of thermo-sensitive formulations with favorable mechanical properties at 37 °C, which formed non-irritant, mucoadhesive porous networks, facilitating nasal RS delivery. Moreover, sustained release of RS, augmented permeability and marked anti-osteoporotic efficacy as compared to intranasal (IN) and intravenous (IV) RS solutions were realized. The combined results show that the in situ gels should have promising application as nasal drug delivery systems.

Well-Defined Star-Shaped Polyglutamates with Improved Pharmacokinetic Profiles As Excellent Candidates for Biomedical Applications.

There is a need to develop new and innovative polymer carriers to be used as drug delivery systems and/or imaging agents owing to the fact that there is no universal polymeric system that can be used in the treatment of all diseases. Additionally, limitations with existing systems, such as a lack of biodegradability and biocompatibility, inevitably lead to side effects and poor patient compliance. New polymer therapeutics based on amino acids are excellent candidates for drug delivery, as they do not suffer from these limitations. This article reports on a simple yet powerful methodology for the synthesis of 3-arm star-shaped polyglutamic acid with well-defined structures, precise molecular weights (MW), and low polydispersity (D = <1.3). These were synthesized by ring-opening polymerization (ROP) of N-carboxyanhydrides (NCA) in a divergent method from novel multifunctional initiators. Herein, their exhaustive physicochemical characterization is presented. Furthermore, preliminary in vitro evaluation in selected cell models, and exhaustive in vivo biodistribution and pharmacokinetics, highlighted the advantages of these branched systems when compared with their linear counterparts in terms of cell uptake enhancement and prolonged plasma half-life.

Photo-crosslinked fabrication of novel biocompatible and elastomeric star-shaped inositol-based polymer with highly tunable mechanical behavior and degradation.

Biodegradable and star-shaped polymers with highly tunable structure and properties have attracted much attention in recent years for potential biomedical applications, due to their special structure. Here, inositol-based star-shaped poly-L-lactide-poly(ethylene glycol) (INO-PLLA-PEG) biomedical polymer implants were for the first time synthesized by a facile photo-crosslinking method. This biomaterials show controlled elastomeric mechanical properties (~18 MPa in tensile strength, ~200 MPa in modulus, ~200% in elongation), biodegradability and osteoblasts biocompatibility. These results make INO-PLLA-PEG implants highly promising for bone tissue regeneration and drug delivery applications.

Simultaneous Nano- and Microscale Control of Nanofibrous Microspheres Self-Assembled from Star-Shaped Polymers.

Star-shaped polymers with varying arm numbers and arm lengths are synthesized, and self-assembled into microspheres, which are either smooth or fibrous on the nanoscale, and either nonhollow, hollow, or spongy on the microscale. The molecular architecture and functional groups determine the structure on both length scales. This exciting mechanistic discovery guides simultaneous control of both the nano- and microfeatures of the microspheres.

Star-Shaped and Linear POSS-Polylactide Hybrid Copolymers.

Novel octakis-2[(6-hydroxyhexyl)thio]ethyl-octasilsesquioxane (POSS-S-OH) as well as heptaisobutyl-2[(6-hydroxyhexyl)thio]ethyl-octasilsesquioxane (iBu-POSS-S-OH) were synthesized. POSS structures, bearing both types of groups i.e., 2[(6-hydroxyhexyl)thio]ethyl and the vinyl ones, pendant from the octahedral cage are also described. The synthetic pathway involved thiol-ene click reaction of 6-mercapto-1-hexanol (MCH) to octavinyloctasilsesquioxane (POSS-Vi), and heptaisobutylvinyloctasilsesquioxane (iBu-POSS-Vi), in the presence of 2,2'-azobisisobutyronitrile. The functionalized silsesquioxane cages of regular octahedral structure were used further as initiators for ring opening polymerization of L,L-dilactide, catalyzed by tin (II) 2-ethylhexanoate. The polymerization afforded biodegradable hybrid star shape and linear systems with an octasilsesquioxane cage as a core, bearing polylactide arm(s).

White polymer light-emitting diodes based on star-shaped polymers with an orange dendritic phosphorescent core.

A series of new star-shaped polymers with a triphenylamine-based iridium(III) dendritic complex as the orange-emitting core and poly(9,9-dihexylfluorene) (PFH) chains as the blue-emitting arms is developed towards white polymer light-emitting diodes (WPLEDs). By fine-tuning the content of the orange phosphor, partial energy transfer and charge trapping from the blue backbone to the orange core is realized to achieve white light emission. Single-layer WPLEDs with the configuration of ITO (indium-tin oxide)/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)/polymer/CsF/Al exhibit a maximum current efficiency of 1.69 cd A(-1) and CIE coordinates of (0.35, 0.33), which is very close to the pure white-light point of (0.33, 0.33). To the best of our knowledge, this is the first report on star-shaped white-emitting single polymers that simultaneously consist of fluorescent and phosphorescent species.

Star-shaped poly(styrene)-block-poly(4-vinyl-N-methylpyridiniumiodide) for semipermanent antimicrobial coatings.

Goal of the present work is to develop an antimicrobial coating that can be applied from an aqueous solution and resists short washing cycles, but can be rinsed off by thorough washing. To this end, a series of star-shaped polystyrene-block-poly(4-vinyl-N-methylpyridinium iodide) polymers are synthesized by anionic polymerization using a core-first approach. The optimal resulting polymers are applied as coatings on glass slides, showing high antimicrobial efficiency against Staphylococcus aureus as well as Escherichia coli. The coatings, characterized by atomic force microscopy and transmission electron microscopy, stay at the surface even after at least 20 flush-like washings with water, and retain their antimicrobial activity.