Search

The composition and structure of polymers have great influence on their performances.

Polymerization-induced self-assembly (PISA) has been demonstrated to be a powerful strategy to produce polymeric nano-objects of various morphologies.

Polymerization-induced self-assembly (PISA) has been established as an efficient method to fabricate polymeric vesicles. In most PISA cases, the formation of vesicles is solely driven by the solvop...

In comparison with the post-polymerization cross-linking strategy, in situ cross-linking by divinyl comonomers in polymerization-induced self-assembly (PISA) is a more straightforward and convenient approach to produce structurally stabilized nano-objects. However, cross-linking usually lowers the chain mobility and hence prevents morphology transition, so formation of higher order morphologies (worm-like micelles or vesicles) by the in situ cross-linking strategy in PISA has always been a great challenge. In this work, not only cross-linked structures but also a promoting effect on morphology transition has been observed during the in situ cross-linking PISA. Worm-like micelles, lamella and vesicles with stabilized (cross-linked) structures are produced by RAFT dispersion copolymerization of 2-(diisopropylamino)ethyl methacrylate (DIPEMA) and the divinyl comonomer cystaminebismethacrylamide (CBMA). The morphology transition is not prevented due to the slower consumption of CBMA than that of the DIPEMA, and the cross-linking process is mostly delayed to the late stage of polymerization. What is surprising, compared with RAFT dispersion polymerization of DIPEMA in the absence of CBMA, is that polymeric nano-objects with higher order morphologies are generated in most cases of the RAFT dispersion copolymerization of DIPEMA and CBMA. The slower consumption of CBMA generates branched structures of the solvophobic blocks, which significantly promote the morphology transition. Cleavage of the cross-linkers (disulfide linkage) by incubating with glutathione (GSH) leads to the morphology transition of the nano-objects to the lower order ones, which further demonstrates the promoting effect on morphology transition in in situ cross-linking PISA.

A multicyclic polymer with a hyperbranched structure was successfully synthesized. A tailored initiator containing a protected alkynyl group was prepared and used to initiate the atom transfer radical polymerization (ATRP) of styrene. By the combination of a click reaction, a UV-induced coupling reaction and post-modification, an AB2 type cyclic polystyrene with a protected alkynyl group and two azide groups was obtained, and after deprotection, the clickable cyclic polymer was used as a macromonomer to prepare a multicyclic polymer with a hyperbranched structure by click polymerization via the AB2 strategy. Gel permeation chromatography (GPC) results showed that the obtained hyperbranched multicyclic polymer contained 47 cyclic units on average.

The development of controlled/“living” polymerization greatly stimulated the prosperity of the fabrication and application of block copolymer nano-objects. Controlled/“living” polymerization was later extended to the scope of polymerization-induced self-assembly (PISA), in which a linear increase of the solvophobic blocks resulted in systemic variation of the packing parameter and almost ergodic morphology transitions. PISA combines polymerization and self-assembly in a much concentrated solution, which has been demonstrated to be a powerful strategy for fabricating block copolymer nano-objects. Various controlled/“living” polymerization techniques, such as reversible addition–fragmentation chain transfer (RAFT) polymerization, nitroxide-mediated polymerization (NMP), atom transfer radical polymerization (ATRP), “living” anionic polymerization, and ring-opening metathesis polymerization (ROMP), have been used in PISA to date. In this review, we summarize the developments of polymerization techniques in PISA, which complementarily enlarge the scope of PISA to a broad range of reaction conditions and monomer families.

A new strategy combing quantitative reactions and reversible-covalent chemistry is proposed for sequential synthesis of a series of sequence-controlled polymers with different sequences. Using a Michael addition reaction between acrylate and thiol, an aminolysis reaction of five-membered cyclic dithiocarbonate and a thiol substitution reaction of bromomaleimide and thiol, AB-, AB'C- and AB'CD-sequenced molecules are synthesized via AB, AB'C and AB'CD sequential monomer additions, respectively. These three molecules all have furan-protected maleimido group at one end, and the other end of AB-, AB'C- and AB'CD-sequenced molecules is amine, thiol and anthracene groups, respectively. Due to the fact that the furan-protected maleimido group can be efficiently transformed to maleimide group at high temperature via retro Diels-Alder reaction, AB-, AB'C- and AB'CD-sequenced molecules polymerize into sequence-controlled polymers with corresponding sequences at 120 °C. Through this strategy, the synthesis of molecular modules does not require separation and purification, and sequence-controlled polymers with specific sequence can be synthesized in a one-pot process via adding different monomers and adjusting reaction condition.

Stimuli-responsive polymeric vesicles have attracted great attention in drug delivery due to their intrinsic hollow structures and “on demand” release of drugs upon environmental stimuli. The drug-release kinetics from polymeric vesicles, which is usually dependent on the stimuli-responsive behaviors of the polymeric vesicle, has great impacts on the therapeutic efficacy. Over the past decade, polymerization-induced self-assembly (PISA) has been demonstrated to be a powerful strategy to prepare the polymeric vesicles. However, fabrication of stimuli-responsive vesicles with adjustable drug release kinetics via PISA has been rarely reported, which may be due to the poor selectivity of functional membrane-forming polymers in the PISA system. Herein, a series of vesicles with different pH-responsive behaviors were fabricated via RAFT dispersion copolymerization of (diisopropylamino)ethyl methacrylate (DIPEMA) and benzyl methacrylate (BzMA). Both the content of DIPEMA units in hydrophobic P(DIPEMA-co-BzMA) bl...

The size and shape of polymeric vesicles have great impact on their physicochemical and biological properties. Polymerization-induced self-assembly (PISA) is an efficient method to fabricate vesicles. In most PISA-cases, the formation of vesicles is driven by the solvophobic interactions which are lack of versatility on finely structural regulation. Herein, controlling vesicular size and shape is realized in PISA aided by aromatic interactions. Aromatic interactions between the membrane-forming blocks contribute to the augments of membrane tension which lead to the formation of smaller vesicles (as small as 70 nm), but overly enhanced aromatic interactions result in vesicle fusion rather than size decreasing. When the membrane tension is dominated by aromatic interactions and meanwhile high enough to overcome the energetic barriers of fusion, the aromatic interactions drive vesicle fusion in a directional manner to form tubular structures. The precise regulation of vesicular size and shape in PISA would pave the way to fabricate vesicles for a series of size/shape-dependent applications.

Polymerization-induced self-assembly (PISA) has been established as a powerful strategy for fabrication of polymeric nano-objects in the past decade. However, in comparison with the traditional self-assembly method, PISA is unsatisfactory in preparation of vesicles with chemical versatility of membrane-forming block for tunable membrane properties, which limits the further application of PISA-based vesicles. Besides the stimuli-responsive property, structural integrity of the vesicles is another important concern for material applications. In situ cross-linking in PISA via copolymerization with multivinyl comonomers (cross-linkers) seems to be a straightforward and convenient method to afford stabilized nano-objects. However, it is hard to fabricate vesicles with cross-linked membrane via in situ cross-linking strategy because cross-linking greatly limits chain mobility of the produced copolymers and thus prevents morphology transition to form vesicles. In this article, in situ cross-linking in PISA for f...

In order to develop pH- and redox-responsive unimolecular micelles composed of camptothecin (CPT)-conjugated hyperbranched star copolymers via acid-labile β-thiopropionate linkage, a new monomer, methacryloyloxy-3-thiohexanoyl–CPT, is synthesized through conjugation of CPT with methacrylate via β-thiopropionate linkage, and then used in synthesis of the CPT-conjugated hyperbranched star copolymers by two steps of atom transfer radical polymerization (ATRP): self-condensation vinyl polymerization of the CPT-based monomer, 2-hydroxypropyl methacrylate and inimer, and subsequent ATRP of oligo(ethylene glycol) methacrylate using the obtained hyperbranched polymers as the macroinitiator. The obtained polymers dissolve in water to form unimolecular micelles, and their release of CPT in water at various pHs and their anticancer efficacy are studied. The CPT-loaded unimolecular micelles with diameters of 3.56–6.08 nm are quite stable under neutral environment, and are easily triggered by mild acidic pH, such as 6.0 and 5.0. They can be easily internalized by the tumor cells, releasing the CPT. The CPT-conjugated unimolecular micelles via acid-labile β-thiopropionate linkage have potential for application as tumor-targeted drug release systems.

Multicyclic polystyrene (PS) with hyperbranched structure was constructed in an efficient way. First, a seesaw-type PS was synthesized via atom transfer radical polymerization (ATRP) using a Y-shaped ATRP initiator containing one hydroxyl at center and bromine at each end. After azidation, the anthryl and hydroxyl groups were introduced to the ends of the polymer chain by click reaction with a trifunctional molecule bearing alkynyl, hydroxyl, and anthryl groups (alkynyl-OH-ant). By irradiation with 365 nm UV light in a highly dilute condition, cyclic polymer with three hydroxyl groups (c-PS-(OH)3) can be obtained; then it was converted to a cyclic polymer containing three azides (c-PS-(N3)3) by bromination of the hydroxyl groups and azidation. This “A3” cyclic macromonomer was then used to construct hyperbranched multicyclic polymers via self-accelerating click reaction with sym-dibenzo-1,5-cyclooctadiene-3,7-diyne (DBA). The properties of obtained polymer were characterized by NMR, FT-IR, MALDI-TOF MS, a...

In this study, an efficient method is proposed for the synthesis of polymer prodrug with acid-liable linkage via thiol-acrylate Michael addition reaction of the camptothecin with tethering acrylate group and polymer scaffold containing multiple thiol groups. The polymer scaffold P(HEO2MA)- b-P(HEMA-DHLA) is prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization of the methacrylate of lipoic acid (HEMA-LA) using poly(2-(2-hydroethoxy) ethyl methacrylate) (PHEO2MA) as macro-RAFT agent followed by reduction of the disulfides in lipoic acid (LA) groups to give polymer scaffold with dihydrolipoic acid (DHLA) pendent groups. Acrylate-tethering camptothecin (ACPT) is connected to P(HEO2MA)- b-P(HEMA-DHLA) via Michael addition reaction between thiol and acrylate with a high coupling efficiency (95%). Amphiphilic polymer prodrug P(HEO2MA)- b-P(HEMA-DHLA-CPT) spontaneously self-assembles into nanoparticles in an aqueous solution and exhibits a CPT loading content as high as 40.1%. The prodrug nanoparticles with the acid-liable β-thiopropionate linkages can release CPT under acidic conditions, and the prodrug nanoparticles show similar cytotoxicity to HeLa cells as free CPT. Overall, the prodrug nanoparticles with high drug loading contents and acid-liable linkages are promising for pH-responsive anticancer therapy.

Although the preparation of nano-objects by emulsifier-free controlled/living radical emulsion polymerization has drawn much attention, the morphologies of these formed objects are difficult to predict and to reproduce because of the much more complex nucleation mechanisms of emulsion polymerization compared to only one self-assembling nucleation mechanism of controlled radical dispersion polymerization. The present study compares dispersion polymerization with emulsifier-free emulsion polymerization in terms of nucleation mechanism, polymerization kinetics, and disappearance behavior of the macrochain transfer agent, gel permeation chromatograms curves of the obtained block copolymer as well as the structural and morphological differences between the produced nano-objects on the basis of published data. Moreover, the effects of the inherently heterogeneous nature of emulsion polymerization on the mechanism of reversible addition-fragmentation transfer polymerization and the nano-object morphology are examined, and efficient agitation and adequate solubility of the core-forming monomer in water are identified as the most crucial factors for the fabrication of nonspherical nano-objects.

A hybrid drug delivery system was successfully fabricated by attaching a camptothecin (CPT)-based polymeric prodrug onto the surface of silver nanoparticles (AgNPs). PEG was employed as a macro-RAFT agent in RAFT polymerization to synthesize a branched star copolymer, to which CPT is linked through the photo-responsive o-nitrobenzyl linkage. In vitro tests indicate that the fluorescence of CPT in the polymeric prodrug is quenched by AgNPs based on the nanomaterial surface energy transfer (NSET) effect and the fluorescence recovers when the CPT molecules are released from hybrid nanoparticles. Thus, the variation of fluorescence intensity is bound up with the drug release behaviours, which may enable this AgNP-based drug delivery system to trace the intracellular drug release process and observe the distribution of released CPT in cells.

By combination of high trapping radical efficiency of thioketone with resonance of allylic radicals, a novel mediated agent, 1, 3, 3-triphenylprop-2-ene-1-thione (TPPT) has been successfully synthesized. 1H NMR method was used to trace the TPPT-mediated radical polymerization of butyl acrylate (BA) at 50 °C, we observed that the disappearance rates of BA, TPPT and initiator, dimethyl 2,2′-azobis (2-methylpropionate) (AIBME) have the following order: BA > AIBME > TPPT, monomer conversion increases gradually with proceeding of the polymerization and approximately 84% of conversion was obtained within 24 h of the polymerization. The molecular weights of the obtained PBA are not varied obviously with the conversion, but the molecular weight distributions are narrow. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) studies reveal three polymerization mechanisms. The TPPT can efficiently capture the growing PBA radicals to form PBA-TPPT• radicals, and this highly stable radicals are able to be cross-terminated by the growing PBA• radicals or primary radicals to form the dormant chains. Although the reversed reaction of reaction 1 is very slow, the extension polymerization of the PBA can undergo to form block copolymers. The molecular weight of the formed PBA is influenced by the feed molar ratio of BA/TPPT and TPPT/AIBME.

A unique drug delivery system, in which silver nanoparticles (AgNPs) are covered with camptothecin (CPT)-based polymer prodrug, has been developed, and the polymer prodrug, in which the CPT is linked to the polymer side chains via an acid-labile β-thiopropionate bond, is prepared by RAFT polymerization. For poly(2-(2-hydroxyethoxy)ethyl methacrylate-co-methacryloyloxy-3-thiahexanoyl-camptothecin)@AgNPs [P(HEO2MA-co-MACPT)@AgNPs], the polymer thickness on the AgNP surface is around 5.9 nm (TGA method). In vitro tests in buffer solutions at pH = 7.4 reveal that fluorescence of the CPT in the hybrid nanoparticles is quenched due to the nanoparticle surface energy transfer (NSET) effect, but under acidic conditions, the CPT fluorescence is gradually recovered with gradual release of the CPT molecules from the hybrid nanoparticles through cleavage of the acid-labile bond. The NSET “on” and “off” is induced by the CPT–AgNP distance change. This unique property makes it possible to track the CPT delivery and rel...

Intelligent vesicles are fabricated at up to 30% solid content via an approach of polymerization-induced self-assembly and reorganization (PISR). Upon irradiation with UV light (365 nm), light-triggered dimerization of the coumarin moieties anchored in the membrane leads to the membrane cross-linking of the vesicles, which endows the vesicles with superior structural stability. Due to the tertiary amine groups in the membrane, the vesicles go through a swelling/deswelling change upon switching the pH values. In acidic aqueous solution, the pores in the membrane of vesicles are opened, which is beneficial for transmembrane traffic. The pore size in the membrane of vesicles is in accordance with the extent of membrane cross-linking, which can be conveniently regulated by the irradiation time of UV light (365 nm). The size range of the substance for transmembrane traffic is effectively enlarged; even 15 nm gold nanoparticles can be postloaded into the vesicles with lower extents of the membrane cross-linking through the diffusion method. Although the pores in the vesicle membrane are opened in acidic aqueous solution, transmembrane traffic is inhibited for the electropositive substance because of electrostatic repulsion but is allowed for the electronegative substance. These reported vesicles herein may be the smartest artificial vesicles to date due to their multiple selective permeability.

CO

A simple and efficient method to construct a hyperbranched multicyclic polymer is introduced. First, a tailored trithiocarbonate with two terminal anthracene units and three azide groups is successfully synthesized, and this multifunctional trithiocarbonate is used as chain transfer agent (CTA) to afford anthracene-telechelic polystyrene (PS) via reversible addition-fragmentation chain transfer (RAFT) polymerization. After that, linear PS is irradiated under 365 nm UV light to achieve the cyclization process. The monocyclic polymer further reacts with sym-dibenzo-1,5-cyclooctadiene-3,7-diyne via "A2 +B3 " strategy based on a self-accelerating click reaction to produce hyperbranched multicyclic polymer. The structures and properties of the polymers are characterized by nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), UV-vis spectrophotometry, and triple-detection size-exclusion chromatography (TD-SEC). The number of monocyclic units of the resultant hyperbranched multicyclic polymer reaches about 21 based on multi-angle laser light scattering (MALLS) measurements. The plot of intrinsic viscosity versus molecular weight reveals that the α value of the unique hyperbranched multicyclic polymer is lower than both hyperbranched polymers and cyclic polymers.

Polymerization-induced self-assembly (PISA) is an efficient and robust strategy to fabricate polymeric nano-objects. PISA enables us to prepare polymeric nano-objects in situ during the course of polymerization in concentrated solution (up to 50% w/w), making industrial production of polymeric assemblies in large-scale possible. In this work, reversible addition-fragmentation chain transfer (RAFT) dispersion copolymerization of styrene (St) and N-methacryloxysuccinimide (NMAS) was conducted with poly(2-hydroxyethyl acrylate) (PHEA) as a macro-chain transfer agent (macro-CTA) in methanol. Compared with the PHEA-mediated alcoholic dispersion polymerization of St, RAFT dispersion copolymerization of St and NMAS promoted morphology transition of nano-objects to form higher order morphologies (such as worms and vesicles). Moreover, the introduction of NMAS units into the solvophobic blocks provided functional handles for post-PISA modification of the resultant nano-objects via the active ester-amine reaction. The reaction of 1,6-hexanediamine with NMAS units in P(St-co-NMAS) blocks was conducted to afford cross-linked nano-objects with robust structural stability.

A visible light mediated reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of benzyl methacrylate (BzMA) is conducted in ethanol using poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) as a macro-chain transfer agent (macro-CTA), affording polymeric nanomaterials with various morphologies. Unlike the polymerization-induced self-assembly and reorganization (PISR) process initiated by thermal stimuli, the photo-controlled PISR can be performed under more mild conditions, such as visible light and room temperature. Photoredox catalysis is employed to regulate the polymerization via a photoinduced electron transfer (PET) process. It is observed that the polymerization can be affected by catalyst concentration and light intensity, and “ON/OFF” control over polymerization is also demonstrated.

A highly efficient strategy, polymerization-induced self-assembly (PISA) for fabrication of the polymeric drug delivery systems in cancer chemotherapy is reported. Diblock prodrug copolymer, PEG-b-P(MEO2MA-co-CPTM) was used as the macro-RAFT agent to fabricate prodrug nanoparticles through PISA. The advantages of fabricating intelligent drug delivery system via this approach are as following: (1) Simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation in one-pot at relatively high concentration (100 mg/mL); (2) Almost complete monomer conversion allows direct application of the resultant prodrug nanoparticles without further purification; (3) Robust structures of the resultant prodrug nanoparticles, because the cross-linker was used as the comonomer, resulted in core-cross-linking simultaneously with the formation of the prodrug nanoparticles; (4) The drug content in the resultant prodrug nanoparticles can be accurately modulated just via adjusting the feed molar ratio of MEO2MA/CPTM in the synthesis of PEG-b-P(MEO2MA-co-CPTM). The prodrug nanoparticles with similar diameters but various drug contents were obtained using different prodrug macro-CTA. In consideration of the long-term biological toxicity, the prodrug nanoparticles with higher drug content exhibit more excellent anticancer efficiency due to that lower dosage of them are enough for effectively killing HeLa cells.

Reversible addition–fragmentation chain transfer (RAFT) dispersion copolymerization of styrene (St) and methyl methacrylate (MMA) is conducted in methanol using poly(2-hydroxyethyl acrylate) (PHEA) as a macro chain transfer agent (macro-CTA). Compared with the general macro-CTA mediated alcoholic dispersion polymerization of St, RAFT dispersion copolymerization of St and MMA can promote the morphology transition of di-block copolymer nano-objects. Three phase diagrams are constructed by changing the molar ratio of St/MMA to reflect the relationship between the degree of polymerization (DP) of P(St-co-MMA), solids concentration and morphology of obtained nano-materials, and it is found that the phase diagrams could be affected by the molar ratio of St/MMA. Ultra-sensitive differential scanning calorimetry (US-DSC) is employed to determine the glass transition temperature (Tg) of polymeric nano-objects in methanol, and the result shows that the Tg values decrease with the increase of the molar content of MMA units in copolymers. Introduction of MMA units into the solvophobic block can enhance its mobility in methanol, which is beneficial for the morphology transition of di-block copolymer nano-objects.

This work presents a facile method to prepare Au–polymer hybrid microgels through thermo-induced self-crosslinking and in situ reduction of a gold precursor. Self-assembly of poly(2-dimethylaminoethyl methacrylate-co-3-(trimethoxysilyl)propyl methacrylate) (P(DMAEMA-co-TMSPMA)) produced particles by heating the P(DMAEMA-co-TMSPMA) solution above the lower critical solution temperature (LCST), which were subsequently cross-linked via the hydrolysis and condensation of the methoxysilyl groups to form microgels. The polymer microgels can be used as a reducing agent for in situ reduction of a gold precursor and a stabilizing agent of gold nanoparticles, leading to the formation of Au–polymer hybrid microgels. The size of the Au–polymer hybrid microgels can be adjusted by varying the concentration of the polymer solution. Furthermore, Au–polymer hybrid microgels were used as a catalyst for the reduction of 4-nitrophenol, which exhibited catalytic performance and reusability towards the reaction.

Cyclic polystyrene (PS) with a pendant coumarin group is prepared by the combination of atom transfer radical polymerization and "click" chemistry. Fluorescence resonance energy transfer process is observed in the fluorescence measurement of coumarin-containing PS, and cyclic PS exhibits stronger emission than that of its linear precursor. When cyclic PS is irradiated under UV light at λ = 365 nm, 8-shaped PS is achieved due to the dimerization of pendant coumarin group. Subsequently, 8-shaped PS can be divided into single macrocycle under UV irradiation at λ = 254 nm via the photocleavage of coumarin dimer. The photoinduced coupling and dissociation are monitored by UV/vis spectra and gel permeation chromatography (GPC).

Graft copolymers with pendant macrocycles were synthesized via “graft onto” method. First, cyclic polystyrene (PS) was achieved by the combination of atom transfer radical polymerization (ATRP) and Cu-catalyzed azide–alkyne cycloaddition (CuAAc), and then an alkynyl group was introduced to cyclic PS. Meanwhile, poly(3-azide-2-hydroxypropyl methacrylate) (PGMA-N 3 ) was synthesized by ATRP of glycidyl methacrylate (GMA) and successive ring-opening of pendant epoxide ring with NaN 3 . The graft copolymer was achieved by the following click reaction between PGMA-N 3 and alkynyl-containing cyclic PS. GPC and 1 H NMR were utilized to characterize the obtained graft copolymers, and a maximal grafting density of 20% was observed. Thermal behaviors of linear PS, cyclic PS and PGMA grafted with cyclic PS (PGMA-g-cPS) were investigated by differential scanning calorimeter (DSC), and T g of PGMA-g-cPS is higher than those of linear and cyclic PS.

A novel nanocontainer, which has silica nanotube (SNT) core and pH-sensitive polymer shell attaching on the exterior surface of silica nanotube, is presented in this paper. Polymer nanorods, which are conveniently fabricated though polymerization-induced self-assembly and reorganization method, are used as templates for the deposition of silica to fabricate hybrid nanorods. Calcination of as-synthesized silica hybrid nanorods leads to hollow SNTs. SNTs are functionalized with reversible addition-fragmentation chain transfer (RAFT) agent, then surface RAFT polymerization is conducted to get poly(2-(diethylamino)ethyl methacrylate)-b-poly(oligo(ethylene glycol) methacrylate)-coated SNTs (SNT-PDEAEMA-b-POEGMA). Doxorubicin (DOX) can be encapsulated in SNT-PDEAEMA-b-POEGMA, and controlled release of loaded DOX is achieved by adjusting pH of the medium. In vitro cell viability and cellular internalization study confirm the potential application of this nanocontainer in drug and gene delivery.

Thermo-responsive Au–polymer hybrid microgels were prepared by a facile temperature-induced co-aggregation and self-crosslinking (TICASC) method, needing no complex operations such as preforming of microgels or prior modification of GNPs. The hybrid microgels were utilized as catalysts for the reduction of 4-nitrophenol, which exhibited good activity and recyclability.

Multi-compartmental cylindrical microstructures with lots of nanotubes on their surface, whose shape resembles a sea cucumber, have been fabricated for the first time. This hierarchical morphology is formed through transitions of vesicles to large compound vesicles, to sea cucumber-like hierarchical microstructures. Along with the morphology transitions, aggregation of the residual polymer chains in the solution occurs, which is called multi-step self-assembling. The driving force of the phase transitions and the multistep self-assembling is polymerization because with the progress of the polymerization, the chain length ratio of PS to P4VP increases, which induces self-assembling and morphology transitions. The requisite for multi-step self-assembling is a high concentration of the P4VP-PS chains remaining in the solution after formation of the nascent assemblies. The concentration of the residual block chains can be controlled by varying the recipe and content of the ethanol. Thus, this study provides a unique strategy to fabricate useful hierarchical assemblies.

An ingenious formulation of RAFT dispersion polymerization based on photosensitive monomers of 2-nitrobenzyl methacrylate (NBMA) and 7-(2-methacryloyloxy-ethoxy)-4-methyl-coumarin (CMA) is reported herein. Various morphologies, such as spherical micelle, nanoworm, lamella, and vesicle, are fabricated at up to 20% solids content. Photoinduced cleavage of the NBMA moieties and dimerization of the coumarin moieties are simultaneously triggered upon UV (365 nm) irradiation. The former endows the cores of the nano-objects with abundant carboxyl groups, resulting in the transformation of the hydrophobic cores to hydrophilic ones. The latter induces the core-cross-linking of the nano-objects, which endows the nano-objects with enhanced structural stability and prevents the nanoparticle-to-unimer disassembly. The resultant nano-objects exhibit superior structural stability and excellent performances for drug delivery, including high drug loadings, pH-stimuli release, and high-efficient endosomal escape.

Different from concentric vesicles without spacing between the walls, the concentric vesicles with uniform spacing between the walls were rarely fabricated. We successfully fabricate the spaced concentric vesicles (SCVs) via RAFT dispersion polymerization, and continuous propagation of the residual polymer chains inside the large vesicles induces self-assembling to form SCVs. Concentration of the residual polymer chains in the solution of the nascent-formed vesicles is the determining factor for formation of SCVs, and continuous propagation of less or too more residual polymer chains will not form SCVs but form other morphologies. Generally, the concentration of the residual polymer chains after formation of vesicles is too low to self-assemble, so formation of SCVs is impossible. By adjusting the ratio of St/methanol or macro-RAFT agent P4VP-b-PS/P4VP, the concentration of residual polymer chains can be controlled, and further control of the morphologies is achieved. Formation of the inner vesicles by se...

Redox-responsive amphiphilic diblock copolymers, poly(6-O-methacryloyl-D-galactopyranose-co-2-(N,N-dimethylaminoethyl) methacrylate)-b-poly(pyridyl disulfide ethyl methylacrylate) (P(MAGP-co-DMAEMA)-b-PPDSMA) were obtained by deprotection of poly((6-O-methacryloyl-1,2:3,4-di-O-isopropylidene-D-galactopyranose)-co-DMAEMA)-b-PPDSMA [P(MAlpGP-co-DMAEMA)-b-PPDSMA], which were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization of PDSMA using P(MAlpGP-co-DMAEMA) as macro-RAFT agent. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies showed that diblock copolymers P(MAGP-co-DMAEMA)-b-PPDSMA can self-assemble into micelles. Doxorubicin (DOX) could be encapsulated by P(MAGP-co-DMAEMA)-b-PPDSMA upon micellization and released upon adding glutathione (GSH) into the micelle solution. The galactose functional groups in the PMAGP block had specific interaction with HepG2 cells, and P(MAGP-co-DMAEMA)-b-PPDSMA can act as gene delivery vehicle. So, this kind of polymer has potential applications in hepatoma-targeting drug and gene delivery and biodetection.

Differently from bulk, solution, suspension, emulsion, and miniemulsion polymerizations, the controlled radical dispersion polymerization (CRDP) demonstrates self-assembly of the block copolymers formed in the homogeneous system, forming various kinds of micelles or vesicles. Thus, this technology can prepare both the block copolymers and the polymeric aggregates directly. Among CRDP, the reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization has been studied in relative detail and has been successfully developed to prepare a diverse range of assemblies. Several typical systems for RAFT dispersion polymerization are presented in detail and the factors influencing the polymerization and the in situ self-assembly are also highlighted in this minireview.

To study the influence of self-assembled morphologies on drug delivery, four different nano-objects, spheres, nanorods, nanowires, and vesicles having aldehdye-based polymer as core, were successfully prepared via alcoholic RAFT dispersion polymerization of p-(methacryloxyethoxy)benzaldehyde (MAEBA) using poly((N,N'-dimethylamino)ethyl methacrylate) (PDMAEMA) as a macro chain transfer agent (macro-CTA) for the first time. The morphologies and sizes of the four nano-objects were characterized by TEM and DLS, and the spheres with average diameter (D) of 70 nm, the nanorods with D of 19 nm and length of 140 nm, and the vesicles with D of 137 nm were used in the subsequent cellular internalization, in vitro release, and intracellular release of the drug. The anticancer drug doxorubicin (DOX) was conjugated onto the core polymers of nano-objects through condensation reaction between aldehyde groups of the PMAEBA with primary amine groups in the DOX. Because the aromatic imine is stable under neutral conditions, but is decomposed in a weakly acidic solution, in vitro release of the DOX from the DOX-loaded nano-objects was investigated in the different acidic solutions. All of the block copolymer nano-objects show very low cytotoxicity to HeLa cells up to the concentration of 1.2 mg/mL, but the DOX-loaded nano-objects reveal different cell viability and their IC50s increase as the following order: nanorods-DOXvesicles-DOXspheres-DOX. The IC50 of nanowires-DOX is the biggest among the four nano-objects owing to their too large size to be internalized. Endocytosis tests demonstrate that the internalization of vesicles-DOX by the HeLa cells is faster than that of the nanorods-DOX, and the spheres-DOX are the slowest to internalize among the studied nano-objects. Relatively more nanorods localized in the acidic organelles of the HeLa cells lead to faster intracellular release of the DOX, so the IC50 of nanorods is lower than that of the vesicles-DOX.

Diverse nanostructural materials including spheres, nanorods, vesicles, and large compound vesicles have been created via formation of amphiphilic ABA triblock copolymers, self-assembling and morphology transition in the reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization. The polymerization of styrene (St) was performed in a selective solvent, methanol, using S,S′-bis(α,α′-dimethyl-α′′-acetic acid)-trithiocarbonate terminated poly(N,N-dimethylacrylamide) (PDMAa-TC) as macro chain transfer agent and stabilizer, and 1H NMR, and TEM were used to monitor the polymerization.

A novel double-hydrophilic block copolymer P(MEO2MA-co-OEGMA)-b-PAMA has been successfully synthesized by two-step RAFT polymerization. Then, the amino groups of PAMA blocks in the copolymers react with 1-pyrenecarboxaldehyde via a “Schiff-base” reaction, and the resulting copolymers are self-assembled to form spherical micelles in aqueous solution. Because the “Schiff-base” linkage is pH sensitive, the release rate of pyrene depends upon the pH of solution. Complete release is achieved at pH 1, and the control release is much faster at pH 5.5 than that at pH 7.4. With progress of pyrene release, the micelles are disassembled gradually and disappeared completely at last. This double-hydrophilic copolymer is a promising candidate of drug carrier for the aldehyde- containing hydrophobic drugs.

A novel nanocontainer, which could regulate the release of payloads, has been successfully fabricated by attaching zwitterionic sulfobetaine copolymer onto the mesoporous silica nanoparticles (MSNs). RAFT polymerization is employed to prepare the hybrid poly(2-(dimethylamino)ethyl methacrylate)-coated MSNs (MSN-PDMAEMA). Subsequently, the tertiary amine groups in PDMAEMA are quaternized with 1,3-propanesultone to get poly(DMAEMA-co-3-dimethyl(methacryloyloxyethyl)ammonium propanesulfonate)-coated MSNs [MSN-Poly(DMAEMA-co-DMAPS)]. The zwitterionic PDMAPS component endows the nanocarrier with biocompatibility, and the PDMAEMA component makes the copolymer shell temperature-responsive. Controlled release of loaded rhodamine B has been achieved in the saline solutions.

Thermoresponsive double hydrophilic diblock copolymers poly(2-(2′-methoxyethoxy)ethyl methacrylate-co-oligo(ethylene glycol) methacrylate)-b-poly(6-O-methacryloyl-D-galactopyranose) (P(MEO2MA-co-OEGMA)-b-PMAGP) with various compositions and molecular weights were obtained by deprotection of amphiphilic diblock copolymers P(MEO2MA-co-OEGMA)-b-poly(6-O-methacryloyl-1,2:3,4-di-O-isopropylidene-D-galactopyranose) (P(MEO2MA-co-OEGMA)-b-PMAlpGP), which were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization using P(MEO2MA-co-OEGMA) as macro-RAFT agent. Dynamic light scattering and UV–vis studies showed that the micelles self-assembled from P(MEO2MA-co-OEGMA)-b-PMAlpGP were thermoresponsive. A hydrophobic dye Nile Red could be encapsulated by block copolymers P(MEO2MA-co-OEGMA)-b-PMAGP upon micellization and released upon dissociation of the formed micelles under different temperatures. The galactose functional groups in the PMAGP block have specific interaction with HepG2 cells, and P(MEO2MA-co-OEGMA)-b-PMAGP has potential applications in hepatoma-targeting drug delivery and biodetection. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

The assembly behavior of diblock copolymers in solution can be modulated by block length, block ratio, solvent properties, and preparation route. Different assembly morphologies such as spherical micelles, cylindrical micelles, vesicles, and large compound vesicles have been obtained for diblock copolymers with shorter solvated block, such as poly(acrylic acid)-b-polystyrene (PAA-b-PSt). In the present work, we reported an easy-going route to prepare PAA-b-PSt assemblies with different morphologies through reversible addition−fragmentation-transfer (RAFT) dispersion polymerization of styrene in methanol with trithiocarbonated PAA as macromolecular chain transfer agent. Because this RAFT dispersion polymerization exhibited controlled features, the consecutive growth of PSt block led to the successive transition of the obtained PAA-b-PSt assemblies from spherical micelles, cylindrical micelles, vesicles, to large compound vesicles, confirmed by the combination of electron microscopy, laser light scattering,...

We investigated the effects of molecular weight and film thickness on the crystallization and microphase separation in semicrystalline block copolymer polystyrene-block-poly(L-lactic acid) (PS-b-PLLA) thin films, at the early stage of film evolution (when Tg < T < TODT) by in situ hot stage atomic force microscopy. For PS-b-PLLA 1 copolymer which had lower molecular weight and higher PLLA fraction, diffusion-controlled break-out crystallization started easily. For PS-b-PLLA 2 with higher molecular weight, crystallization in nanometer scales occurs in local area. After melting of the two copolymer films, islands were observed at the film surface: PS-b-PLLA 1 film was in a disordered phase mixed state while PS-b-PLLA 2 film formed phase-separated lamellar structure paralleling to the substrate. Crystallization-melting and van der Waals forces drove the island formation in PS-b-PLLA 1 film. Film thickness affected the crystallization rate. Crystals grew very slowly in much thinner film of PS-b-PLLA 1 and remained almost unchanged at long time annealing. The incompatibility between PS and PLLA blocks drove the film fluctuation which subsequently evolved into spinodal-like morphology.

Carbon nanotubes (CNTs) are of increasing interest to scientists because of their unique electronic, chemical and mechanical properties. However, the poor solubility in solvents limits the manipulation of CNTs and hampers their applications in many promising fields. Surface modification of CNTs with polymers is an efficient method to solve this problem. In comparison with linear polymers, dendrimers and hyperbranched polymers are highly branched macromolecules with three-dimensional architecture, and they have good solubility, low melt viscosity, and extremely high density of functional groups at the surface. By surface modification with dendrimers or hyperbranched polymers, the solubility of CNTs could be improved greatly. Moreover, the resultant composites can be endowed with novel properties by further functionalization, which enlarges the applications of CNTs. This review makes emphasis on discussing the methods for functionalization of CNTs with dendrimers or hyperbranched polymers, meanwhile, the unique properties and potential applications of the resultant composites are also summarized in an attempt to facilitate the progress in this interesting area.

Various morphologies including spherical micelles, nanowires and vesicles have been prepared by reversible addition-fragmentation chain transfer (RAFT) dispersion polymerization of styrene (St) in methanol using S-1-dodecyl-S -(α,α′-dimethyl-α″-acetic acid) trithiocarbonate (TC)-terminated poly(ethylene oxide) (PEO-TC) and 2,2′-azobis(isobutyronitrile) (AIBN) as chain transfer agent and initiator, respectively. GPC, 1H NMR, TEM and laser light scattering (LLS) were used to track the polymerization. The results showed that the block copolymers PEO-b-polystyrene (PEO-b-PS) were formed firstly in homogenous polymer solution, and then the spherical micelles were produced via polymerization-induced self-assembling. Continuous polymerization of the PS blocks induced the transition of spherical micelles into other morphologies. The polymerization-induced self-assembling and reorganization (PISR) were induced by chain length ratio increase of PS to PEO blocks. The concentration of St in methanol is also important factor to influence the formation of morphologies.